Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium
Open accessAbstract
Intestinal epithelial cells (IEC) are organised as a single cell layer which covers the intestine. Their primary task is to absorb nutrients present in the intestinal lumen. However, IEC also play an important role in the immune defence of our body by building a barrier that separates the bowel wall from potentially hazardous bacteria present in the gut lumen. The life cycle of IEC is determined by the time span in which cells migrate from their place of origin at the crypt base to the villus tip, from where they are shed into the lumen. Cell death in the intestinal epithelium has to be tightly regulated and irregularities might cause pathologies. Excessive cell death has been associated with chronic inflammation as seen in patients with Crohn's disease and ulcerative colitis. While until recently apoptosis was discussed as being essential for epithelial turnover and tissue homeostasis in the intestinal epithelium, recent data using gene deficient mice have challenged this concept. Moreover, an apoptosis-independent mode of programmed cell death, termed necroptosis, has been identified and described in the intestinal epithelium. The following article reviews previous studies on cell death regulation in IEC and a potential role of necroptosis for gut homeostasis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis.
“Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis.”
From Programmed cell death in aging (2015) · cites this paper as Gunther et al., 2013
In the adult, PCD is required for the normal turnover of cells in numerous tissues that are maintained by cell division, including the intestinal epithelium, the blood, the epidermis, kidney and lungs.
“In the adult, PCD is required for the normal turnover of cells in numerous tissues that are maintained by cell division, including the intestinal epithelium, the blood, the epidermis, kidney and lungs(Elmore, 2007; Gunther et al., 2013; Kile, 2014).”
From Programmed cell death in aging (2015) · cites this paper as Gunther et al., 2013
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial
Hanauer, S. B., Feagan, B. G., Lichtenstein, G. R., Mayer, L., Schreiber, S., Colombel, J., Rachmilewitz, D., Wolf, D. C., Olson, A. D., Bao, W., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08512-4 · Cited by 4,164 · see citing works
Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury
Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N., Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., & Yuan, J. (2005) · Nature Chemical Biology · doi:10.1038/nchembio711 · Cited by 3,068 · see citing works
Muzio, M., Chinnaiyan, A. M., Kischkel, F. C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J. D., Zhang, M., Gentz, R., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81266-0 · Cited by 3,046 · see citing works
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes
Micheau, O., & Tschopp, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00521-x · Cited by 2,738 · see citing works
Inhibition of death receptor signals by cellular FLIP
Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J.-L., Schröter, M., Burns, K., Mattmann, C., et al. (1997) · Nature · doi:10.1038/40657 · Cited by 2,548 · see citing works
Cho, Y., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., & Chan, F. K.-M. (2009) · Cell · doi:10.1016/j.cell.2009.05.037 · Cited by 2,435 · see citing works
Molecular mechanisms of necroptosis: an ordered cellular explosion
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T., & Kroemer, G. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2970 · Cited by 2,382 · see citing works
Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to TNF-α
He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., & Wang, X. (2009) · Cell · doi:10.1016/j.cell.2009.05.021 · Cited by 2,214 · see citing works
Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.-L., Schneider, P., Seed, B., & Tschopp, J. (2000) · Nature Immunology · doi:10.1038/82732 · Cited by 1,932 · see citing works
RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Zhang, D.-W., Shao, J., Lin, J., Zhang, N., Lu, B.-J., Lin, S.-C., Dong, M.-Q., & Han, J. (2009) · Science · doi:10.1126/science.1172308 · Cited by 1,931 · see citing works
Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice
Kuida, K., Zheng, T. S., Na, S., Kuan, C.-Y., Yang, D., Karasuyama, H., RAKIC, P. T., & Flavell, R. A. (1996) · Nature · doi:10.1038/384368a0 · Cited by 1,881 · see citing works
Intestinal homeostasis and its breakdown in inflammatory bowel disease
Maloy, K., & Powrie, F. (2011) · Nature · doi:10.1038/nature10208 · Cited by 1,865 · see citing works
Stem cells, self-renewal, and differentiation in the intestinal epithelium.
van der Flier, L. G., & Clevers, H. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163145 · Cited by 1,859 · see citing works
Metastasis: a question of life or death
Mehlen, P., & Puisieux, A. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1886 · Cited by 1,854 · see citing works
Hanauer, S. B., Sandborn, W. J., Rutgeerts, P. J., Fedorak, R. N., Lukáš, M., MacIntosh, D. G., Panaccione, R., Wolf, D. C., & Pollack, P. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.030 · Cited by 1,711 · see citing works
Kaser, A., Lee, A.-H., Franke, A., Glickman, J., Zeissig, S., Tilg, H., Nieuwenhuis, E., Higgins, D. E., Schreiber, S., Glimcher, L., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.021 · Cited by 1,442 · see citing works
Intestinal Goblet Cells and Mucins in Health and Disease: Recent Insights and Progress
Kim, Y. S., & Ho, S. B. (2010) · Current Gastroenterology Reports · doi:10.1007/s11894-010-0131-2 · Cited by 1,437 · see citing works
Varfolomeev, E., Schuchmann, M., Luria, V., Chiannilkulchai, N., Beckmann, J., Mett, I., Rebrikov, D., Brodianski, V. M., Kemper, O., Kollet, O., et al. (1998) · Immunity · doi:10.1016/s1074-7613(00)80609-3 · Cited by 1,332 · see citing works
The fundamental basis of inflammatory bowel disease
Strober, W., Fuss, I. J., & Mannon, P. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30587 · Cited by 1,310 · see citing works
Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis
Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C., Hakem, R., Salvesen, G. S., & Green, D. R. (2011) · Nature · doi:10.1038/nature09852 · Cited by 1,278 · cited 5× · see citing works
“Interestingly, it turns out that there is a high degree of overlap in the molecules that regulate apoptosis and necroptosis.59 65 91e95 Under physiological conditions, TNFR ligation results in the assembly of one of the following complexes: the TNFR complex I which mediates survival functions and involves the molecule…”
BackgroundInfluentialRegulation and Function of IKK and IKK-Related Kinases
Häcker, H., & Karin, M. (2006) · Science s STKE · doi:10.1126/stke.3572006re13 · Cited by 1,269 · see citing works
Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis
Bevins, C. L., & Salzman, N. H. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2546 · Cited by 1,238 · see citing works
Certolizumab Pegol for the Treatment of Crohn's Disease
Sandborn, W. J., Feagan, B. G., Stoinov, S., Honiball, P., Rutgeerts, P. J., Mason, D. H., Bloomfield, R., & Schreiber, S. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa067594 · Cited by 1,141 · see citing works
Epithelial NEMO links innate immunity to chronic intestinal inflammation
Nenci, A., Becker, C., Wullaert, A., Gareus, R., Loo, G., Danese, S., Huth, M., Nikolaev, A., Neufert, C. F., Madison, B., et al. (2007) · Nature · doi:10.1038/nature05698 · Cited by 1,077 · see citing works
Self-citationRIP3 mediates the embryonic lethality of caspase-8-deficient mice
Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., Hakem, R., Caspary, T., & Mocarski, E. S. (2011) · Nature · doi:10.1038/nature09857 · Cited by 1,057 · see citing works
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing
Pickert, G., Neufert, C., Leppkes, M., Zheng, Y., Wittkopf, N., Warntjen, M., Lehr, H.-A., Hirth, S., Weigmann, B., Wirtz, S., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20082683 · Cited by 1,043 · see citing works
Self-citationHitomi, J., Christofferson, D. E., Ng, A., Yao, J., Degterev, A., Xavier, R. J., & Yuan, J. (2008) · Cell · doi:10.1016/j.cell.2008.10.044 · Cited by 989 · see citing works
Bollrath, J., Phesse, T. J., von Burstin, V. A., Putoczki, T., Bennecke, M., Bateman, T., Nebelsiek, T., Lundgren-May, T., Canli, Ö., Schwitalla, S., et al. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.002 · Cited by 946 · see citing works
Vercammen, D., Beyaert, R., Denecker, G., Goossens, V., Loo, G., Declercq, W., Grooten, J., Fiers, W., & Vandenabeele, P. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.9.1477 · Cited by 925 · see citing works
Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis.
Laster, S. M., Wood, J. G., & Gooding, L. R. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.8.2629 · Cited by 909 · see citing works
Etanercept for active Crohn's disease: A randomized, double-blind, placebo-controlled trial
Sandborn, W. J., Hanauer, S. B., Katz, S., Safdi, M. A., Wolf, D. G., Baerg, R. D., Tremaine, W. J., Johnson, T., Diehl, N. N., & ZINSMEISTER, A. R. (2001) · Gastroenterology · doi:10.1053/gast.2001.28674 · Cited by 906 · see citing works
Fas and Fas ligand: lpr and gld mutations
Nagata, S., & Suda, T. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80069-7 · Cited by 900 · see citing works
FADD: Essential for Embryo Development and Signaling from Some, But Not All, Inducers of Apoptosis
Yeh, W., de la Pompa, J. L., McCurrach, M. E., Shu, H., Elia, A., Shahinian, A., Ng, M. S. W., Wakeham, A. C., Khoo, W., Mitchell, K., et al. (1998) · Science · doi:10.1126/science.279.5358.1954 · Cited by 886 · see citing works
Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis
Günther, C., Martini, E., Wittkopf, N., Amann, K., Weigmann, B., Neumann, H., Waldner, M. J., Hedrick, S. Μ., Tenzer, S., Neurath, M. F., et al. (2011) · Nature · doi:10.1038/nature10400 · Cited by 882 · see citing works
Self-citationFeoktistova, M., Geserick, P., Kellert, B., Panayotova‐Dimitrova, D., Langlais, C., Hupe, M., Cain, K., MacFarlane, M., Häcker, G. A., & Leverkus, M. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.011 · Cited by 855 · see citing works
Cleavage of the death domain kinase RIP by Caspase-8 prompts TNF-induced apoptosisPreprint
Lin, Y., Devin, A., Rodriguez, Y., & Liu, Z.-G. (1999) · Genes & Development · doi:10.1101/gad.13.19.2514 · Cited by 835 · see citing works
Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changesPreprint
Woo, M., Hakem, R., Soengas, M. S., Duncan, G. S., Shahinian, A., Kägi, D., Hakem, A., McCurrach, M. E., Khoo, W., Kaufman, S. A., et al. (1998) · Genes & Development · doi:10.1101/gad.12.6.806 · Cited by 832 · see citing works
The Role of c-FLIP in Modulation of CD95-induced Apoptosis
Scaffidi, C., Schmitz, I., Krammer, P. H., & Peter, M. E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.3.1541 · Cited by 819 · see citing works
Death receptor-induced cell killing
Thorburn, A. M. (2003) · Cellular Signalling · doi:10.1016/j.cellsig.2003.08.007 · Cited by 787 · see citing works
Necroptosis as an alternative form of programmed cell death
Christofferson, D. E., & Yuan, J. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.12.003 · Cited by 771 · see citing works
Organizing cell renewal in the intestine: stem cells, signals and combinatorial control
Crosnier, C., Stamataki, D., & Lewis, J. H. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1840 · Cited by 756 · see citing works
Necrosis: a specific form of programmed cell death?
Proskuryakov, S., Konoplyannikov, A. G., & Gabai, V. L. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00027-7 · Cited by 721 · see citing works
Role of cytokines in inflammatory bowel disease
Sanchez-Muñoz, F., Dominguez-Lopez, A., & Yamamoto-Furusho, J. K. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4280 · Cited by 699 · see citing works
Tumour necrosis factor alpha in stool as a marker of intestinal inflammation
Braegger, C., Nicholls, S. J., MURCH, S. H., MacDonald, T. T., & Stephens, S. (1992) · The Lancet · doi:10.1016/0140-6736(92)90999-j · Cited by 683 · see citing works
Life and death in peripheral T cells
Krammer, P. H., Arnold, R., & Lavrik, I. N. (2007) · Nature reviews. Immunology · doi:10.1038/nri2115 · Cited by 652 · see citing works
Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features
Berghe, T. V., Vanlangenakker, N., Parthoens, E., Deckers, W., Devos, M., Festjens, N., Guerin, C. J., Brunk, U. T., Declercq, W., & Vandenabeele, P. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.184 · Cited by 639 · see citing works
Barker, N., van de Wetering, M., & Clevers, H. (2008) · Genes & Development · doi:10.1101/gad.1674008 · Cited by 629 · see citing works
FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation
Welz, P.-S., Wullaert, A., Vlantis, K., Kondylis, V., Fernández-Majada, V., Ermolaeva, M., Kirsch, P., Sterner-Kock, A., van Loo, G., & Pasparakis, M. (2011) · Nature · doi:10.1038/nature10273 · Cited by 594 · see citing works
RIP Kinase-Dependent Necrosis Drives Lethal Systemic Inflammatory Response Syndrome
Duprez, L., Takahashi, N., Hauwermeiren, F. V., Vandendriessche, B., Goossens, V., Berghe, T. V., Declercq, W., Libert, C., Cauwels, A., & Vandenabeele, P. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.020 · Cited by 591 · see citing works
Nazli, A., Chan, O., Dobson-Belaire, W. N., Ouellet, M., Tremblay, M. J., Gray‐Owen, S. D., Arsenault, A. L., & Kaushic, C. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000852 · Cited by 591 · see citing works
The intestinal epithelial stem cell
Marshman, E., Booth, C., & Potten, C. S. (2002) · BioEssays · doi:10.1002/bies.10028 · Cited by 588 · see citing works
Breese, E. J., Michie, C. A., Nicholls, S. W., MURCH, S. H., Williams, C. B., Domizio, P., Walker-Smith, J. A., & MacDonald, T. T. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90398-0 · Cited by 566 · see citing works
Krueger, A., Schmitz, I., Baumann, S., Krammer, P. H., & Kirchhoff, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101780200 · Cited by 565 · see citing works
c‐FLIPL is a dual function regulator for caspase‐8 activation and CD95‐mediated apoptosis
Chang, D. W.-W., Xing, Z., Pan, Y., Algeciras‐Schimnich, A., Barnhart, B. C., Yaish‐Ohad, S., Peter, M. E., & Yang, X. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf356 · Cited by 560 · see citing works
Regulation of tissue homeostasis by NF-κB signalling: implications for inflammatory diseases
Pasparakis, M. (2009) · Nature reviews. Immunology · doi:10.1038/nri2655 · Cited by 523 · see citing works
Yeh, W.-C., Itie, A., Elia, A. J., Ng, M., Shu, H.-B., Wakeham, A., Mirtsos, C., Suzuki, N., Bonnard, M., Goeddel, D. V., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)80214-9 · Cited by 515 · see citing works
Rioux, J. D., Silverberg, M. S., Daly, M. J., Steinhart, A. H., McLeod, R. S., Griffiths, A. M., Green, T. J., Brettin, T. S., Stone, V., Bull, S. B., et al. (2000) · The American Journal of Human Genetics · doi:10.1086/302913 · Cited by 498 · see citing works
Caspase 8 inhibits programmed necrosis by processing CYLD
O’Donnell, M. A., Perez-Jimenez, E., Oberst, A., Ng, A., Massoumi, R., Xavier, R., Green, D. R., & Ting, A. T. (2011) · Nature Cell Biology · doi:10.1038/ncb2362 · Cited by 494 · see citing works
Lavrik, I. N., Golks, A., & Krammer, P. H. (2005) · Journal of Cell Science · doi:10.1242/jcs.01610 · Cited by 494 · see citing works
MacDonald, T. T., Hutchings, P. R., CHOY, M.-Y., et al. (1990) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1990.tb03334.x · Cited by 483 · see citing works
The Long Form of FLIP Is an Activator of Caspase-8 at the Fas Death-inducing Signaling Complex
Micheau, O., Thome, M., Schneider, P., Holler, N., Tschopp, J., Nicholson, D. W., Briand, C., & Grütter, M. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206882200 · Cited by 482 · see citing works
Functional biology of intestinal goblet cells
Specian, R. D., & Oliver, M. G. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.260.2.c183 · Cited by 468 · see citing works
Chan, F. K.-M., Shisler, J. L., Bixby, J. G., Felices, M., Zheng, L., APPEL, M. C., Orenstein, J. O., Moss, B., & Lenardo, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305633200 · Cited by 463 · see citing works
Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain
Feng, S., Yang, Y., Mei, Y., Ma, L., Zhu, D.-E., Höti, N., Castanares, M. A., & Wu, M. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.05.016 · Cited by 445 · see citing works
Porter, E. M., Bevins, C. L., Ghosh, D., & Ganz, T. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8412-z · Cited by 423 · see citing works
Functional complementation between FADD and RIP1 in embryos and lymphocytes
Zhang, H., Zhou, X., McQuade, T. J., Li, J., Chan, F. K.-M., & Zhang, J. (2011) · Nature · doi:10.1038/nature09878 · Cited by 422 · see citing works
Lin, Y., Choksi, S., Shen, H., Yang, Q., Hur, G. M., Kim, Y. S., Tran, J. H., Nedospasov, S. A., & Liu, Z.-G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313141200 · Cited by 411 · see citing works
Sun, X., Yin, J., Starovasnik, M. A., Fairbrother, W. J., & Dixit, V. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109488200 · Cited by 371 · see citing works
Caspase-independent cell death: leaving the set without the final cut
Tait, S. W. G., & Green, D. R. (2008) · Oncogene · doi:10.1038/onc.2008.311 · Cited by 366 · see citing works
Programmed necrosis: backup to and competitor with apoptosis in the immune system
Han, J., Zhong, C., & Zhang, D. (2011) · Nature Immunology · doi:10.1038/ni.2159 · Cited by 365 · see citing works
Molecular Mechanisms and Pathophysiology of Necrotic Cell Death
Vanlangenakker, N., Berghe, T. V., Krysko, D. V., Festjens, N., & Vandenabeele, P. (2008) · Current Molecular Medicine · doi:10.2174/156652408784221306 · Cited by 347 · see citing works
cFLIP regulation of lymphocyte activation and development
Budd, R., Yeh, W., & Tschopp, J. (2006) · Nature reviews. Immunology · doi:10.1038/nri1787 · Cited by 310 · see citing works
Merritt, A. J., Potten, C. S., Watson, A. J. M., et al. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.6.2261 · Cited by 304 · see citing works
Arijs, I., Hertogh, G. D., Lemaire, K., Quintens, R., Lommel, L. V., Steen, K. V., Leemans, P., Cleynen, I., Assche, G. V., Vermeire, S., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007984 · Cited by 304 · see citing works
Alternative cell death mechanisms in development and beyondPreprint
Yuan, J., & Kroemer, G. (2010) · Genes & Development · doi:10.1101/gad.1984410 · Cited by 290 · see citing works
Reimund, J. M., Wittersheim, C., Dumont, S., Muller, C. D., Baumann, R., Poindron, P., & Duclos, B. (1996) · Journal of Clinical Immunology · doi:10.1007/bf01540912 · Cited by 281 · see citing works
The gastrointestinal tract stem cell niche
Yen, T., & Wright, N. A. (2006) · Stem Cell Reviews and Reports · doi:10.1007/s12015-006-0048-1 · Cited by 279 · see citing works
Examining the Role of Paneth Cells in the Small Intestine by Lineage Ablation in Transgenic Mice
Garabedian, E. M., Roberts, L. J., McNevin, M. S., & Gordon, J. I. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23729 · Cited by 279 · see citing works
Marchiando, A. M., Shen, L., Graham, W. V., Edelblum, K. L., Duckworth, C. A., Guan, Y., Montrose, M. H., Turner, J. R., & Watson, A. J. M. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.004 · Cited by 276 · see citing works
Activation of caspases-8 and -10 by FLIPL
Boatright, K. M., Cristina, D. E. I. S., Denault, J., Sutherlin, D. P., & Salvesen, G. S. (2004) · Biochemical Journal · doi:10.1042/bj20040809 · Cited by 242 · see citing works
Komatsu, M., Kobayashi, D., Saito, K., et al. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.7.1297 · Cited by 242 · see citing works
Structure–activity relationship study of novel necroptosis inhibitors
Teng, X., Degterev, A., Jagtap, P. G., Xing, X., Choi, S., Denu, R., Yuan, J., & Cuny, G. D. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.07.077 · Cited by 241 · see citing works
Mechanisms of necroptosis in T cells
Ch’en, I. L., Tsau, J., Molkentin, J. D., Komatsu, M., & Hedrick, S. Μ. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20110251 · Cited by 229 · see citing works
Live and let die in the intestinal epithelium
Sancho, E., Batlle, E., & Clevers, H. C. (2003) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2003.10.012 · Cited by 228 · see citing works
Linkage of Inflammatory Bowel Disease to Human Chromosome 6p
Hampe, J., Shaw, S. H., Saiz, R., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302677 · Cited by 227 · see citing works
Pop, C., Oberst, A., Drąg, M., van Raam, B. J., Riedl, S. J., Green, D. R., & Salvesen, G. S. (2011) · Biochemical Journal · doi:10.1042/bj20101738 · Cited by 225 · see citing works
Epithelial Barrier Function In Vivo Is Sustained Despite Gaps in Epithelial Layers
Watson, A. J. M., Chu, S., Sieck, L., Gerasimenko, O. V., Bullen, T., Campbell, F., McKenna, M. P., Rose, T. L., & Montrose, M. H. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.06.015 · Cited by 215 · see citing works
Characterization of epithelial cell shedding from human small intestine
Bullen, T., Forrest, S. I., Campbell, F., Dodson, A. R., Hershman, M. J., Pritchard, D. M., Turner, J. R., Montrose, M. H., & Watson, A. J. M. (2006) · Laboratory Investigation · doi:10.1038/labinvest.3700464 · Cited by 214 · see citing works
Regulation of Early Wave of Germ Cell Apoptosis and Spermatogenesis by Deubiquitinating Enzyme CYLD
Wright, A., Reiley, W. W., Chang, M., Jin, W., Lee, A. J., Zhang, M., & Sun, S. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.09.007 · Cited by 212 · see citing works
Apoptosis in the intestinal epithelium: Its relevance in normal and pathophysiological conditions
Ramachandran, A., Madesh, M., & Balasubramanian, K. A. (2000) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2000.02059.x · Cited by 211 · see citing works
Regulation of apoptosis during homeostasis and disease in the intestinal epithelium
Edelblum, K. L., Yan, F., Yamaoka, T., & Polk, D. B. (2006) · Inflammatory Bowel Diseases · doi:10.1097/01.mib.0000217334.30689.3e · Cited by 190 · see citing works
Taylor, C. T., Dzus, A. L., & Colgan, S. P. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70579-7 · Cited by 188 · see citing works
Paneth cells: their role in innate immunity and inflammatory disease
Elphick, D. A., & Mahida, Y. R. (2005) · Gut · doi:10.1136/gut.2005.068601 · Cited by 183 · see citing works
Wu, Y., Tan, H.-L., Huang, Q., Xj, S., Zhu, X., & Shen, H.-M. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.72 · Cited by 176 · see citing works
Steinbrecher, K. A., Harmel-Laws, E., Sitcheran, R., & Baldwin, A. S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2588 · Cited by 174 · see citing works
RIPK-Dependent Necrosis and Its Regulation by Caspases: A Mystery in Five Acts
Green, D. R., Oberst, A., Dillon, C. P., Weinlich, R., & Salvesen, G. S. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.09.003 · Cited by 169 · see citing works
Enterocyte death and intestinal barrier maintenance in homeostasis and disease
Vereecke, L., Beyaert, R., & Loo, G. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.05.011 · Cited by 165 · see citing works
Increased Enterocyte Apoptosis in Inflamed Areas of Crohn's Disease
Sabatino, A. D., Ciccocioppo, R., Luinetti, O., Ricevuti, L., Morera, R., Cifone, M. G., Solcia, E., & Corazza, G. R. (2003) · Diseases of the Colon & Rectum · doi:10.1007/s10350-004-6802-z · Cited by 163 · see citing works
It cuts both ways: reconciling the dual roles of caspase 8 in cell death and survival
Oberst, A., & Green, D. R. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3214 · Cited by 157 · see citing works
TUMOUR NECROSIS FACTOR-INDUCED NECROSIS VERSUS ANTI-Fas-INDUCED APOPTOSIS IN L929 CELLS
Vercammen, D., Vandenabeele, P., Beyaert, R., Declercq, W., & Fiers, W. (1997) · Cytokine · doi:10.1006/cyto.1997.0252 · Cited by 157 · see citing works
萩原, 主., Tanaka, M., & Kudo, H. (2002) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2002.02791.x · Cited by 150 · see citing works
Kajino‐Sakamoto, R., Inagaki, M., Lippert, E., Akira, S., Robine, S., Matsumoto, K., Jobin, C., & Ninomiya‐Tsuji, J. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.2.1143 · Cited by 147 · see citing works
Li, M. O., & Beg, A. A. (2000) · Journal of Virology · doi:10.1128/jvi.74.16.7470-7477.2000 · Cited by 144 · see citing works
Ireland, H., Houghton, C. A., Howard, L., & Winton, D. J. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20446 · Cited by 139 · see citing works
Nonapoptotic functions of FADD-binding death receptors and their signaling molecules
Park, S.-M., Schickel, R., & Peter, M. E. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.09.010 · Cited by 138 · see citing works
Chokshi, N. K., Guner, Y. S., Hunter, C. J., Upperman, J. S., Grishin, A., & Ford, H. R. (2008) · Seminars in Perinatology · doi:10.1053/j.semperi.2008.01.002 · Cited by 137 · see citing works
Wehkamp, J., Koslowski, M. J., Wang, G., & Stange, E. F. (2008) · Mucosal Immunology · doi:10.1038/mi.2008.48 · Cited by 136 · see citing works
Strain-Dependent Neurodevelopmental Abnormalities in Caspase-3-Deficient Mice
Leonard, J. R., Klocke, B. J., D’Sa-Eipper, C., Flavell, R. A., & Roth, K. A. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.8.673 · Cited by 135 · see citing works
Paneth cell defensins and the regulation of the microbiome
Salzman, N. H. (2010) · Gut Microbes · doi:10.4161/gmic.1.6.14076 · Cited by 128 · see citing works
Epistatic and independent functions of Caspase-3 and Bcl-X L in developmental programmed cell death
Roth, K. A., Kuan, C.-Y., Haydar, T. F., D’Sa-Eipper, C., Shindler, K. S., Zheng, T. S., Kuida, K., Flavell, R. A., & RAKIC, P. T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.1.466 · Cited by 119 · see citing works
Grossmann, J., Mohr, S., Lapetina, E. G., Fiocchi, C., & Levine, A. D. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.274.6.g1117 · Cited by 119 · see citing works
Glimcher, L. H. (2009) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2009.119388 · Cited by 116 · see citing works
Epithelial integrity, cell death and cell loss in mammalian small intestine.
Mayhew, T. M., Myklebust, R., Whybrow, A., & Jenkins, R. (1999) · PubMed · doi:10.14670/hh-14.257 · Cited by 114 · see citing works
Non-apoptotic functions of caspase-8
Maelfait, J., & Beyaert, R. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.07.034 · Cited by 113 · see citing works
Ultrastructure of cell loss in intestinal mucosa
Potten, C. S., & Allen, T. D. (1977) · Journal of Ultrastructure Research · doi:10.1016/s0022-5320(77)80071-3 · Cited by 113 · see citing works
Paesold, G., Guiney, D. G., Eckmann, L., et al. (2002) · Cellular Microbiology · doi:10.1046/j.1462-5822.2002.00233.x · Cited by 105 · see citing works
Ismail, A. S., & Hooper, L. V. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00203.2005 · Cited by 103 · see citing works
Necrosis Is an Active and Controlled Form of Programmed Cell Death
Proskuryakov, S. Y., Gabai, V. L., & Konoplyannikov, A. (2002) · Biochemistry (Moscow) · doi:10.1023/a:1015289521275 · Cited by 94 · see citing works
VII. Apoptosis in intestinal epithelium: lessons from transgenic and knockout mice
Watson, A. J. M., & Pritchard, D. M. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.278.1.g1 · Cited by 92 · see citing works
Proliferative versus apoptotic functions of caspase-8
van Raam, B. J., & Salvesen, G. S. (2011) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2011.06.005 · Cited by 90 · see citing works
The fate of epithelial cells in the human large intestine
Barkla, D. H., & Gibson, P. R. (1999) · Pathology · doi:10.1080/003130299105043 · Cited by 88 · see citing works
New therapeutic strategies for treatment of inflammatory bowel disease
Atreya, R. N., & Neurath, M. F. (2008) · Mucosal Immunology · doi:10.1038/mi.2008.7 · Cited by 82 · see citing works
Self-citationDeChairo, B. M., Dimon, C., van Heel, D. A., et al. (2001) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200687 · Cited by 79 · see citing works
Lewin, K. (1969) · Gut · doi:10.1136/gut.10.10.804 · Cited by 74 · see citing works
François, M., Cabec, V. L., Dupont, M.-A., Sansonetti, P. J., & Maridonneau‐Parini, I. (2000) · Infection and Immunity · doi:10.1128/iai.68.3.1289-1296.2000 · Cited by 72 · see citing works
Caspase deficiency alters the murine gut microbiome
Brinkman, B. M., Hildebrand, F., Kubica, M., Goosens, D., Del Favero, J., Declercq, W., Raes, J., & Vandenabeele, P. (2011) · Cell Death & Disease · doi:10.1038/cddis.2011.101 · Cited by 70 · see citing works
Necrosis and apoptosis in the gastrointestinal tract.
Watson, A. J. M. (1995) · Gut · doi:10.1136/gut.37.2.165 · Cited by 69 · see citing works
Weinlich, R., Dillon, C. P., & Green, D. R. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2011.09.002 · Cited by 68 · see citing works
Molecular Mechanisms of Enteroendocrine Differentiaton
Höcker, M., & Wiedenmann, B. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb11120.x · Cited by 64 · see citing works
The Ripoptosome: Death Decision in the Cytosol
Bertrand, M. J. M., & Vandenabeele, P. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.007 · Cited by 64 · see citing works
The Relevance of Apoptosis for Cellular Homeostasis and Tumorogenesis in the Intestine
Renehan, A. G., Bach, S. P., & Potten, C. S. (2001) · Canadian Journal of Gastroenterology · doi:10.1155/2001/164727 · Cited by 60 · see citing works
REVIEW ARTICLE. p53: GUARDIAN OF CELLULAR SENESCENCE
Wynford‐Thomas, D. (1996) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199610)180:2 · Cited by 59 · see citing works
Apoptosis of intestinal crypt epithelium after Cryptosporidium parvum infection
Sasahara, T., Sekiguchi, T., Sato, Y., et al. (2003) · Journal of Infection and Chemotherapy · doi:10.1007/s10156-003-0259-1 · Cited by 56 · see citing works
Colussi, P. A., & Kumar, S. (1999) · Immunology and Cell Biology · doi:10.1046/j.1440-1711.1999.00788.x · Cited by 54 · see citing works
Role of intestinal lymphatics in interstitial volume regulation and transmucosal water transport
Kvietys, P. R., & Granger, D. N. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05709.x · Cited by 50 · see citing works
Metcalfe, A. D., & Streuli, C. H. (1997) · BioEssays · doi:10.1002/bies.950190812 · Cited by 49 · see citing works
Epithelial patchy necrosis in Crohn's disease
Dourmashiin, R. R., Davies, H. A., Wells, C. W., Shah, D. B., Price, A. B., O'Morain, C. A., & Levi, J. (1983) · Human Pathology · doi:10.1016/s0046-8177(83)80207-x · Cited by 43 · see citing works
Epithelial cell differentiation in normal and transgenic mouse intestinal isografts.
Rubin, D. C., Roth, K. A., Birkenmeier, E. H., et al. (1991) · The Journal of Cell Biology · doi:10.1083/jcb.113.5.1183 · Cited by 42 · see citing works
Emerging Roles for the Death Adaptor FADD in Death Receptor Avidity and Cell Cycle Regulation
Werner, M. H., Wu, C., & Walsh, C. M. (2006) · Cell Cycle · doi:10.4161/cc.5.20.3385 · Cited by 40 · see citing works
Cell death in the colonic epithelium during inflammatory bowel diseases
Chen, L., Park, S.-M., Turner, J. R., & Peter, M. E. (2010) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21191 · Cited by 36 · see citing works
Zachrisson, K., Neopikhanov, V., Samali, A., et al. (2001) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200105000-00015 · Cited by 22 · see citing works
Caprioli, F., Stolfi, C., Caruso, R., et al. (2008) · Gut · doi:10.1136/gut.2008.149286 · Cited by 12 · see citing works
Levy, E. H., & Bendayan, M. (2000) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(20000515)49:4 · Cited by 10 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Ziv E, Bendayan M. Intestinal absorption of peptides through the enterocytes. Microsc Res Tech 2000;49:346e52.
- Iwamoto M, Koji T, Makiyama K, et al. Apoptosis of crypt epithelial cells in ulcerative colitis. J Pathol 1996;180:152e9.
Cited by
Sorted by citations
Programmed cell death in aging
Tower, J. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.04.002 · Cited by 426 · see citing works
Tumour Necrosis Factor Alpha in Intestinal Homeostasis and Gut Related Diseases
Ruder, B., Atreya, R., & Becker, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081887 · Cited by 228 · see citing works
Self-citationUnveiling ferroptosis as a promising therapeutic avenue for colorectal cancer and colitis treatment
Kao, A. T., Cabanlong, C. V., Padilla, K., & Xue, X. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.05.025 · Cited by 30 · see citing works
- Authors
- Günther, C., Neumann, H., Neurath, M. F., & Becker, C.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Corresponding author
- Becker, Christoph
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2012-06-11
- Volume
- 62
- Issue
- 7
- Pages
- 1062-1071
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2167862372
- Cited by
- 462
- References
- 143
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 54 · 2023: 43 · 2022: 48 · 2021: 57 · 2020: 41 · 2019: 34 · 2018: 24 · 2017: 24 · 2016: 22 · 2015: 27 · 2014: 24 · 2013: 8 · 2012: 2
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- green
- open.fau.de
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- apoptosis, necrosis, necroptosis, intestinal epithelial cells, cell death regulation, intestinal homeostasis, epithelial cell turnover, intestinal barrier, Crohn's disease, ulcerative colitis, chronic intestinal inflammation, programmed cell death
- MeSH terms
- Cell Cycle, Epithelial Cells, Humans, Intestinal Mucosa, Necrosis, Inflammatory Bowel Diseases, Cell Death, Apoptosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review