Alternative Proteolytic Processing of Hepatocyte Growth Factor during Wound Repair
Open accessAbstract
Wound healing is a crucial regenerative process in all organisms. We examined expression, integrity, and function of the proteins in the hepatocyte growth factor (HGF)/c-Met signaling pathway in normally healing and non-healing human skin wounds. Whereas in normally healing wounds phosphorylation of c-Met was most prominent in keratinocytes and dermal cells, in non-healing wounds phosphorylation of c-Met was barely detectable, suggesting reduced c-Met activation. In wound exudates obtained from non-healing, but not from healing wounds, HGF protein was a target of substantial proteolytic processing that was different from the classical activation by known serine proteases. Western blot analysis and protease inhibitor studies revealed that HGF is a target of neutrophil elastase and plasma kallikrein during skin repair. Proteolytic processing of HGF by each of these proteases significantly attenuated keratinocyte proliferation, wound closure capacity in vitro, and c-Met signal transduction. Our findings reveal a novel pathway of HGF processing during skin repair. Conditions in which proteases are imbalanced and tend toward increased proteolytic activity, as in chronic non-healing wounds, might therefore compromise HGF activity due to the inactivation of the HGF protein and/or the generation of HGF fragments that ultimately mediate a dominant negative effect and limit c-Met activation.
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?
In chronic wounds, there is a marked increase in serine proteases that degrade matrix components including fibronectin and key growth factors required for extracellular matrix remodeling and cell growth.
“Last, in chronic wounds, there is a marked increase in serine proteases that degrades matrix components, including fibronectin, as well as various key growth factors, all of which are required for remodeling of the ECM and cell growth (38-41).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [40]
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
Gurtner, G. C., Werner, S., Barrandon, Y., & Longaker, M. T. (2008) · Nature · doi:10.1038/nature07039 · Cited by 6,542 · see citing works
Regulation of Wound Healing by Growth Factors and Cytokines
WERNER, S., & GROSE, R. (2003) · Physiological Reviews · doi:10.1152/physrev.2003.83.3.835 · Cited by 3,629 · see citing works
Inflammation in Wound Repair: Molecular and Cellular Mechanisms
Eming, S. A., Krieg, T., & Davidson, J. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700701 · Cited by 2,429 · see citing works
Self-citationScatter factor/hepatocyte growth factor is essential for liver development
Schmidt, C. S., Bladt, F., Gödecke, S., Brinkmann, V., Zschiesche, W., Sharpe, M. J., Gherardi, E., & Birchmeler, C. (1995) · Nature · doi:10.1038/373699a0 · Cited by 1,395 · see citing works
Bussolino, F., Di Renzo, M. F., Ziche, M., Bocchietto, E., Olivero, M., Naldini, L., Gaudino, G., Tamagnone, L., Coffer, A., & Comoglio, P. M. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.629 · Cited by 1,337 · see citing works
Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud
Bladt, F., Riethmacher, D., Isenmann, S., Aguzzi, A., & Birchmeier, C. (1995) · Nature · doi:10.1038/376768a0 · Cited by 1,284 · see citing works
Scatter-factor and semaphorin receptors: cell signalling for invasive growth
Trusolino, L., & Comoglio, P. M. (2002) · Nature reviews. Cancer · doi:10.1038/nrc779 · Cited by 738 · see citing works
Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells.
Weidner, K. M., Behrens, J., Vandekerckhove, J. S., & Birchmeier, W. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.5.2097 · Cited by 684 · see citing works
Fonder, M. A., Lazarus, G. S., Cowan, D. A., Aronson-Cook, B., Kohli, A. R., & Mamelak, A. J. (2008) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2007.08.048 · Cited by 665 · see citing works
Gohda, E., Tsubouchi, H., Nakayama, H., Hirono, S., Sakiyama, O., Takahashi, K., MIYAZAKI, H., Hashimoto, S., & Daikuhara, Y. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113334 · Cited by 656 · see citing works
Naldini, L., Tamagnone, L., Vigna, E., Sachs, M., Hartmann, G. R., Birchmeier, W., Daikuhara, Y., Tsubouchi, H., Blasi, F., & Comoglio, P. M. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05588.x · Cited by 566 · see citing works
Impaired wound healing in mice with a disrupted plasminogen gene
Rømer, J., Bugge, T. H., Fyke, C., Lund, L. R., Flick, M. J., Degen, J. L., & Danø, K. (1996) · Nature Medicine · doi:10.1038/nm0396-287 · Cited by 560 · see citing works
A Signaling Adapter Function for α6β4 Integrin in the Control of HGF-Dependent Invasive Growth
Trusolino, L., Bertotti, A., & Comoglio, P. M. (2001) · Cell · doi:10.1016/s0092-8674(01)00567-0 · Cited by 420 · see citing works
Lee, S.-L., Dickson, R. B., & Lin, C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007802200 · Cited by 393 · see citing works
ONO-5046, a novel inhibitor of human neutrophil elastase
Kawabata, K., Suzuki, M., Sugitani, M., Imaki, K., Toda, M., & Miyamoto, T. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91862-7 · Cited by 359 · see citing works
Expression and Proteolysis of Vascular Endothelial Growth Factor is Increased in Chronic Wounds
Lauer, G., Sollberg, S., Cole, M., Krieg, T., Eming, S. A., Flamme, I., Stürzebecher, J., & Mann, K. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00036.x · Cited by 349 · see citing works
Self-citationc-Met is essential for wound healing in the skin
Chmielowiec, J., Borowiak, M., Morkel, M., Stradal, T. E. B., Munz, B., Werner, S., Wehland, J., Birchmeier, C., & Birchmeier, W. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200701086 · Cited by 320 · see citing works
Ferracini, R., Renzo, M. F. D., Scotlandi, K., Baldini, N., Olivero, M., Lollini, P., Cremona, O., Campanacci, M., & Comoglio, P. M. (1995) · PubMed · Cited by 280 · see citing works
Grinnell, F., & Zhu, M. (1996) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12342990 · Cited by 232 · see citing works
Structural basis of hepatocyte growth factor/scatter factor and MET signalling
Gherardi, E., Sandin, S., Petoukhov, M. V., Finch, J. T., Youles, M. E., Öfverstedt, L., Miguel, R. N., Blundell, T. L., Woude, G. F. V., Skoglund, U., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509040103 · Cited by 224 · see citing works
HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor
Date, K., Matsumoto, K., Shimura, H., Tanaka, M., & Nakamura, T. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01475-0 · Cited by 217 · see citing works
Miyazawa, K., Shimomura, T., & Kitamura, N. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.7.3615 · Cited by 216 · see citing works
Nusrat, A., Parkos, C. A., Bacarra, A. E., Godowski, P. J., Delp-Archer, C., Rosen, E. M., & Madara, J. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117200 · Cited by 209 · see citing works
Hu, B., Guo, P., Bar-Joseph, I., Imanishi, Y., Jarzynka, M. J., Bögler, O., Mikkelsen, T., Hirose, T., Nishikawa, R., & Cheng, S. (2007) · Oncogene · doi:10.1038/sj.onc.1210348 · Cited by 192 · see citing works
Transcriptional Control of Wound Repair
Schäfer, M., & Werner, S. (2007) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.23.090506.123609 · Cited by 187 · see citing works
Shimomura, T., Miyazawa, K., Komiyama, Y., Hiraoka, H., Naka, D., Morimoto, Y., & Kitamura, N. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.0257l.x · Cited by 175 · see citing works
NK4 (HGF‐antagonist/angiogenesis inhibitor) in cancer biology and therapeutics
Matsumoto, K., & Nakamura, T. (2003) · Cancer Science · doi:10.1111/j.1349-7006.2003.tb01440.x · Cited by 153 · see citing works
Herrick, S. E., Ashcroft, G. S., Ireland, G. W., Horan, M. A., McCollum, C. N., & Ferguson, M. W. J. (1997) · PubMed · Cited by 146 · see citing works
Diverse and potent activities of HGF/SF in skin wound repair
Bevan, D., Gherardi, E., Fan, T., Edwards, D. R., & Warn, R. M. (2004) · The Journal of Pathology · doi:10.1002/path.1578 · Cited by 143 · see citing works
Shimomura, T., Miyazawa, K., Komiyama, Y., et al. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20463.x · Cited by 131 · see citing works
Plasmin Modulates Vascular Endothelial Growth Factor-A-Mediated Angiogenesis during Wound Repair
Roth, D., Piekarek, M., Paulsson, M., Christ, H., Bloch, W., Krieg, T., Davidson, J. M., & Eming, S. A. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050372 · Cited by 127 · see citing works
Self-citationConway, K., Price, P., Harding, K. G., & Jiang, W. G. (2006) · Wound Repair and Regeneration · doi:10.1111/j.1743-6109.2005.00081.x · Cited by 121 · see citing works
Parr, C., & Jiang, W. G. (2001) · International Journal of Oncology · doi:10.3892/ijo.19.4.857 · Cited by 115 · see citing works
Eming, S. A., Lee, J., Snow, R. G., Tompkins, R. G., Yarmush, M. L., & Morgan, J. R. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12325550 · Cited by 105 · see citing works
Self-citationEming, S. A., Smola, H., Hartmann, B., Malchau, G., Wegner, R., Krieg, T. M., & Smola, S. (2008) · Biomaterials · doi:10.1016/j.biomaterials.2008.03.029 · Cited by 101 · see citing works
Self-citationYoshida, S., Yamaguchi, Y., Itami, S., Yoshikawa, K., Tabata, Y., Matsumoto, K., & Nakamura, T. (2003) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2003.12039.x · Cited by 100 · see citing works
Holmes, O., Pillozzi, S., Deakin, J. A., Carafoli, F., Kemp, L., Butler, P. J. G., Lyon, M., & Gherardi, E. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.12.061 · Cited by 94 · see citing works
Matsumoto, K., Takehara, T., Inoue, H., Hagiya, M., Shimizu, S., & Nakamura, T. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91246-9 · Cited by 82 · see citing works
Toyoda, M., Takayama, H., Horiguchi, N., Otsuka, T., Fukusato, T., Merlino, G. T., Takagi, H., & Mori, M. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03126-x · Cited by 77 · see citing works
Beilmann, M., Odenthal, M., Jung, W., Woude, G. F. V., Dienes, H., & Schirmacher, P. (1997) · Blood · doi:10.1182/blood.v90.11.4450 · Cited by 75 · see citing works
Peek, M., Moran, P., Mendoza, N., Wickramasinghe, D., & Kirchhofer, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209778200 · Cited by 70 · see citing works
Okigaki, M., Komada, M., Uehara, Y., Miyazawa, K., & Kitamura, N. (1992) · Biochemistry · doi:10.1021/bi00155a007 · Cited by 69 · see citing works
Huttunen, M., & Harvima, I. T. (2005) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2005.06428.x · Cited by 51 · see citing works
Eming, S. A., Smola, S., Kurschat, P., Hirche, D., Krieg, T. M., & Smola, H. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700474 · Cited by 51 · see citing works
Self-citationAdams, J. C., Furlong, R. A., & Watt, F. M. (1991) · Journal of Cell Science · doi:10.1242/jcs.98.3.385 · Cited by 46 · see citing works
Raymond, W. W., Cruz, A. C., & Caughey, G. H. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m511154200 · Cited by 36 · see citing works
Roles of Hepatocyte Growth Factor and Mast Cells in Thrombosis and Angiogenesis
Matsumori, A. (2004) · Cardiovascular Drugs and Therapy · doi:10.1023/b:card.0000041252.33870.74 · Cited by 10 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Nusrat A, Parkos CA, Bacarra AE, Godowski PJ, Delp-Archer C, Rosen EM, Madara JL: Hepatocyte growth factor/scatter factor ef- Processing of HGF in Tissue Repair 2127 AJP June 2009, Vol. 174, No. 6
Cited by
Sorted by citations
Wound repair and regeneration: Mechanisms, signaling, and translation
Eming, S. A., Martin, P., & Tomic-Canic, M. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009337 · Cited by 3,562 · see citing works
Self-citationNeutrophils and Wound Repair: Positive Actions and Negative Reactions
Wilgus, T. A., Roy, S., & McDaniel, J. C. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0383 · Cited by 616 · see citing works
Cytokines, chemokines and growth factors in wound healing
Behm, B., Babilas, P., Landthaler, M., & Schreml, S. (2011) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/j.1468-3083.2011.04415.x · Cited by 419 · see citing works
Eming, S. A., Koch, M., Krieger, A., Brachvogel, B., Kreft, S., Bruckner-Tuderman, L., Krieg, T., Shannon, J. D., & Fox, J. W. (2010) · Journal of Proteome Research · doi:10.1021/pr100456d · Cited by 248 · see citing works
Self-citationContribution of Platelets, the Coagulation and Fibrinolytic Systems to Cutaneous Wound Healing.
Opneja, A., Kapoor, S., & Stavrou, E. (2019) · Thrombosis Research · doi:10.1016/j.thromres.2019.05.001 · Cited by 179 · see citing works
Factor XII and uPAR upregulate neutrophil functions to influence wound healing
Stavrou, E. X., Fang, C., Bane, K. L., Long, A. T., Naudin, C., Kucukal, E., Gandhi, A., Brett-Morris, A., Mumaw, M. M., Izadmehr, S., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci92880 · Cited by 143 · see citing works
Therapeutic role of growth factors in treating diabetic wound
Zheng, S.-Y., Wan, X.-X., Kambey, P. A., Luo, Y., Hu, X., Liu, Y., Shan, J.-Q., Chen, Y., & Xiong, K. (2023) · World Journal of Diabetes · doi:10.4239/wjd.v14.i4.364 · Cited by 140 · see citing works
Molecular Pathophysiology of Chronic Wounds: Current State and Future DirectionsPreprint
Pastar, I., Balukoff, N. C., Marjanović, J., Chen, V. Y., Stone, R. C., & Tomic‐Canic, M. (2022) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041243 · Cited by 122 · see citing works
Roles of Factor XII in Innate Immunity
Renné, T., & Stavrou, E. X. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02011 · Cited by 105 · see citing works
Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing
Volksdorf, T., Heilmann, J., Eming, S. A., Schawjinski, K., Zorn‐Kruppa, M., Ueck, C., Vidal‐y‐Sy, S., Windhorst, S., Jücker, M., Moll, I., et al. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.02.006 · Cited by 102 · see citing works
Self-citationHGF–Met Pathway in Regeneration and Drug Discovery
Matsumoto, K., Funakoshi, H., Takahashi, H., & Sakai, K. (2014) · Biomedicines · doi:10.3390/biomedicines2040275 · Cited by 85 · see citing works
Gacche, R. N., & Meshram, R. J. (2013) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2013.10.001 · Cited by 97 · see citing works
Pathogenesis of wound healing disorders in the elderly
Makrantonaki, E., Wlaschek, M., & Scharffetter‐Kochanek, K. (2017) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/ddg.13199 · Cited by 88 · see citing works
Hepatocyte growth factor and Met in drug discovery
Sakai, K., Aoki, S., & Matsumoto, K. (2015) · The Journal of Biochemistry · doi:10.1093/jb/mvv027 · Cited by 82 · see citing works
Structural basis for agonism and antagonism of hepatocyte growth factor
Tolbert, W. D., Daugherty-Holtrop, J., Gherardi, E., Woude, G. V., & Xu, H. E. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005183107 · Cited by 78 · see citing works
Agarwal, P., Schulz, J.-N., Blumbach, K., Andréasson, K., Heinegård, D. K., Paulsson, M., Mauch, C., Eming, S. A., Eckes, B., & Krieg, T. M. (2013) · Matrix Biology · doi:10.1016/j.matbio.2013.02.010 · Cited by 67 · see citing works
Self-citationThe roles of receptor tyrosine kinases and their ligands in the wound repair process.
Müller, A.-K., Meyer, M., & Werner, S. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.09.015 · Cited by 70 · see citing works
Poindexter, N. J., Williams, R. R., Powis, G., Jen, E. Y., Caudle, A. S., Chada, S., & Grimm, E. A. (2010) · Experimental Dermatology · doi:10.1111/j.1600-0625.2010.01077.x · Cited by 63 · see citing works
Honda, K., Okamoto, K., Mochida, Y., Ishioka, K., Oka, M., Maesato, K., Ikee, R., Moriya, H., Hidaka, S., Ohtake, T., et al. (2011) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00065.2011 · Cited by 56 · see citing works
Mizuno, S., & Nakamura, T. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14010888 · Cited by 52 · see citing works
Anti-inflammatory and anti-arthritic activity in extract from the leaves of Eriobotrya japonica
Kuraoka-Oliveira, Â. M., Radai, J. A. S., Leitão, M. M., Cardoso, C. A. L., Silva-Filho, S. E., & Kassuya, C. A. L. (2019) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2019.112418 · Cited by 50 · see citing works
Trøstrup, H., Lundquist, R., Christensen, L. H., Jørgensen, L. N., Karlsmark, T., Haab, B. B., & Ågren, M. S. (2011) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2011.10384.x · Cited by 49 · see citing works
Pivotal Role for α1-Antichymotrypsin in Skin Repair
Hoffmann, D. C., Textoris, C., Oehme, F., Klaassen, T., Goppelt, A., Römer, A., Fugmann, B., Davidson, J. M., Werner, S., Krieg, T. M., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.249979 · Cited by 46 · see citing works
Self-citationNovak, M. L., Bryer, S. C., Cheng, M., Nguyen, M.-H., Conley, K. L., Cunningham, A. K., Xue, B., Sisson, T. H., You, J., Hornberger, T. A., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1004091 · Cited by 45 · see citing works
Jafari, S. M. S., Shafighi, M., Beltraminelli, H., Geiser, T., Hunger, R. E., & Gazdhar, A. (2017) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000003259 · Cited by 44 · see citing works
Cavassan, N. R. V., Camargo, C., de Pontes, L. G., Barraviera, B., Ferreira, R. S., Miot, H., Abbade, L. P., & dos Santos, L. D. (2019) · Journal of Proteomics · doi:10.1016/j.jprot.2018.09.009 · Cited by 31 · see citing works
Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome
Leung, K., Schaefer, K., Lin, Z., Yao, Z. W., & Wells, J. A. (2025) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00554 · Cited by 39 · see citing works
Xu, Y., Zhao, H., Zheng, Y., Gu, Q., Ma, J., & Xu, X. (2010) · PubMed Central · Cited by 37 · see citing works
Stability of the Cathelicidin Peptide LL-37 in a Non-healing Wound Environment
Grönberg, A., Zettergren, L., & Ågren, M. S. (2011) · Acta Dermato Venereologica · doi:10.2340/00015555-1102 · Cited by 33 · see citing works
Pathogenese von Wundheilungsstörungen bei älteren Patienten
Makrantonaki, E., Wlaschek, M., & Scharffetter‐Kochanek, K. (2017) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1111/ddg.13199_g · Cited by 28 · see citing works
Kroeze, K. L., Vink, L., Boer, E. M. D., Scheper, R. J., van Montfrans, C., & Gibbs, S. (2012) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2012.00789.x · Cited by 28 · see citing works
Pavone, L. M., Cattaneo, F., Rea, S., Pasquale, V. D., Spina, A., Sauchelli, E., Mastellone, V., & Ammendola, R. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.07.005 · Cited by 27 · see citing works
Alpha-1 Antitrypsin Mitigates the Inhibition of Airway Epithelial Cell Repair by Neutrophil Elastase
Garratt, L. W., Sutanto, E. N., Ling, K., Looi, K., Iosifidis, T., Martinovich, K. M., Shaw, N. C., Buckley, A. G., Kicic‐Starcevich, E., Lannigan, F. J., et al. (2015) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2015-0074oc · Cited by 26 · see citing works
Proteomics and Metabolomics forIn SituMonitoring of Wound Healing
Kalkhof, S., Förster, Y., Schmidt, J. R., Schulz, M. C., Baumann, S., Weißflog, A., Gao, W., Hempel, U., Eckelt, U., Rammelt, S., et al. (2014) · BioMed Research International · doi:10.1155/2014/934848 · Cited by 24 · see citing works
High Concentration but Low Activity of Hepatocyte Growth Factor in Periodontitis
Lönn, J., Johansson, C. S., Nakka, S. S., Palm, E. C., Bengtsson, T., Nayeri, F., & Ravald, N. (2013) · Journal of Periodontology · doi:10.1902/jop.2013.130003 · Cited by 23 · see citing works
The epithelialisation phase in wound healing: options to enhance wound closure
Tomic‐Canic, M., Wong, L. L., & Smola, H. (2018) · Journal of Wound Care · doi:10.12968/jowc.2018.27.10.646 · Cited by 21 · see citing works
Self-citationKolditz, F., Krausze, J., Heinz, D. W., Niemann, H. H., & Müller-Goymann, C. C. (2013) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2013.10.003 · Cited by 20 · see citing works
Revolutionizing diabetic wound healing: Targeted therapeutic strategies based on growth factors
Yadav, J. P., Patel, D. K., Verma, A., & Pathak, P. (2024) · Obesity Medicine · doi:10.1016/j.obmed.2024.100535 · Cited by 19 · see citing works
Allosteric Peptide Activators of Pro-Hepatocyte Growth Factor Stimulate Met Signaling
Landgraf, K. E., Santell, L., Billeci, K. L., Quan, C. L., Young, J. C., Maun, H. R., Kirchhofer, D., & Lazarus, R. A. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.179721 · Cited by 19 · see citing works
Wound fluid sampling methods for proteomic studies: A scoping review
Harvey, J., Mellody, K. T., Cullum, N. A., Watson, R. E. B., & Dumville, J. C. (2022) · Wound Repair and Regeneration · doi:10.1111/wrr.13009 · Cited by 17 · see citing works
Identification of Mannose Receptor as Receptor for Hepatocyte Growth Factor β-Chain
Ohnishi, H., Oka, K., Mizuno, S., & Nakamura, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.318568 · Cited by 17 · see citing works
Mikosiński, J., Kalogeropoulos, K., Bundgaard, L., Larsen, C. A., Savickas, S., Haack, A. M., Pańczak, K., Rybołowicz, K., Grzela, T., Olszewski, M., et al. (2022) · Acta Dermato Venereologica · doi:10.2340/actadv.v102.325 · Cited by 15 · see citing works
Self-citationFactor XII in inflammation and wound healing
Stavrou, E. X. (2018) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000450 · Cited by 13 · see citing works
The Involvement of Proteoglycans in the Human Plasma Prekallikrein Interaction with the Cell Surface
Veronez, C. L., Nascimento, F. D., Melo, K. R. B., Nader, H. B., Tersariol, I. L. S., & Motta, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091280 · Cited by 11 · see citing works
Lönn, J., Shahzad, F., Uhlin, F., Bengtsson, T., Almroth, G., & Nayeri, F. (2012) · Advances in Bioscience and Biotechnology · doi:10.4236/abb.2012.324068 · Cited by 9 · see citing works
Clinical assessment of a foam dressing containing growth factor-enhancing hydrated polyurethanes
Mikosiński, J., Kotala, M., Stücker, M., Twardowska-Saucha, K., Bonnekoh, B., Pańczak, K., Aleksiejew-Kleszczyński, T., Dissemond, J., Eming, S. A., Kaspar, D., et al. (2018) · Journal of Wound Care · doi:10.12968/jowc.2018.27.9.608 · Cited by 8 · see citing works
Self-citationA Host-Directed Approach to the Detection of Infection in Hard-to-Heal Wounds
Burnet, M. W. M., Metcalf, D. G., Milo, S., Gamerith, C., Heinzle, A., Sigl, E., Eitel, K., Haalboom, M., & Bowler, P. G. (2022) · Diagnostics · doi:10.3390/diagnostics12102408 · Cited by 8 · see citing works
Paradoxical action of growth factors: antiproliferative and proapoptotic signaling by HGF/c-MET
Grzelakowska-Sztabert, B., & Dudkowska, M. (2011) · Growth Factors · doi:10.3109/08977194.2011.585609 · Cited by 8 · see citing works
Lu, Y., Xu, Y., Gu, Q., & Xu, X. (2015) · Cornea · doi:10.1097/ico.0000000000000548 · Cited by 8 · see citing works
Proteases: Nature’s Destroyers and the Drugs that Stop Them
Veltri, C. A. (2015) · Pharmacy & Pharmacology International Journal · doi:10.15406/ppij.2015.02.00044 · Cited by 7 · see citing works
Zhao, N., Wang, G., Long, S., Lv, X., Ran, X., Wang, J., Su, Y., & Wang, T. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70291 · Cited by 6 · see citing works
Miao, W., Sakai, K., Imamura, R., Ito, K., Suga, H., Sakuma, T., Yamamoto, T., & Matsumoto, K. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103141 · Cited by 6 · see citing works
Oyeyemi, S. O., Averina, M., Huber, S., Charles, D., Furberg, A., Yigzaw, K. Y., Wilsgaard, T., Nielsen, C. S., & Grimnes, G. (2025) · Environmental Research · doi:10.1016/j.envres.2025.122096 · Cited by 3 · see citing works
Eming, S. A., Wlaschek, M., & Scharffetter‐Kochanek, K. (2016) · Der Hautarzt · doi:10.1007/s00105-015-3738-2 · Cited by 3 · see citing works
Self-citationChalenko, Y. M., Владимировна, С. Е., Sobyanin, K. A., Рафаилевна, К. М., Lavrikova, A. Y., Kalinin, E. V., Scheglovitova, O. N., & Ermolaeva, S. A. (2018) · Archives of Dermatological Research · doi:10.1007/s00403-018-1870-4 · Cited by 3 · see citing works
Construction of Agonistic Bivalent Double‐Stranded Aptamers Targeting c‐MET
Zhang, X., Zhang, N., Sun, H., Sheng, J., Li, Y., Long, Z., Liu, X., & Shangguan, D. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.202516203 · Cited by 2 · see citing works
Lönn, J., Nakka, S. S., Olsson, H., Bengtsson, T., Almer, S. H., & Nayeri, F. (2013) · Advances in Bioscience and Biotechnology · doi:10.4236/abb.2013.48a2006 · Cited by 2 · see citing works
An observational study of wounds treated with hydro-responsive wound dressings
Goedecke, F., Bühring, J., Kratz, A., Schweiger, W., Köhle, C., Waidner, U., Riedel, T., Walter, A., Skrowny, P., Rothenaicher, G., et al. (2022) · Journal of Wound Care · doi:10.12968/jowc.2022.31.12.1029 · Cited by 1 · see citing works
Regulation of Hepatocyte Growth Factor in Mice with Pneumonia by Peptidases and Trans-Alveolar Flux
Raymond, W. W., Xu, X. M., Nimishakavi, S., Le, C. T., McDonald, D. M., & Caughey, G. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125797 · Cited by 1 · see citing works
Development of novel wound dressing based on elastin-like recombinamers for skin regeneration
Juanes‐Gusano, D. (2024) · doi:10.35376/10324/71600 · Cited by 1 · see citing works
von Allmen, R. S., & Dick, F. (2014) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2014.07.004
U-251-MG 세포에서 PSA 경로에 작용하는 Hepatocyte Growth Factor의 효과
김환규 (2009) · KSBB Journal
Physiological Roles and Therapeutic Implications of Hepatocyte Growth Factor for Angiogenesis
Ohnishi, H., Mizuno, S., Oka, K., & Nakamura, T. (2013) · Springer eBooks · doi:10.1007/978-1-4614-5857-9_22
Synthesis of small-molecule HGF-Met inhibitors for use in preventing cell motility
BUNTE, A. (2020) · University of Salford Institutional Repository (University of Salford)
Injectable Hydrogels as a Stem Cell Delivery Platform for Wound Healing
Xu, Q., Sigen, A., & Wang, W. (2022) · Wiley eBooks · doi:10.1002/9783527825820.ch14
Construction of Agonistic Bivalent Double‐Stranded Aptamers Targeting c‐MET
Zhang, X., Zhang, N., Sun, H., Sheng, J., Li, Y., Long, Z., Liu, X., & Shangguan, D. (2026) · Angewandte Chemie · doi:10.1002/ange.202516203
Gupta, A., Soman, S., Jadhav, S. R., Marwaha, D., Halagali, P., Saha, M., Mutalik, S., Moorkoth, S., Dhas, N. L., Tippavajhala, V. K., et al. (2026) · OpenNano · doi:10.1016/j.onano.2026.100304
Prakash, S., & Srivastava, S. (2026) · Journal of Tissue Viability · doi:10.1016/j.jtv.2026.101069
- Authors
- Buchstein, N., Hoffmann, D., Smola, H., Lang, S., Paulsson, M., Niemann, C., Krieg, T., & Eming, S. A.
- Affiliations
- University of Cologne (DE)
- Corresponding author
- Eming, Sabine A.
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 174
- Issue
- 6
- Pages
- 2116-2128
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC2684177
- OpenAlex
- W1993493788
- Cited by
- 68
- References
- 46
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 6 · 2020: 1 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 5 · 2013: 8 · 2012: 4
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB829, LSHB-CT-2005-512102)
- Universität zu Köln
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- hepatocyte growth factor, C-MET signaling, wound healing, proteolytic processing, neutrophil elastase, plasma kallikrein, chronic non-healing wounds, keratinocyte proliferation, wound closure, serine protease, dominant negative effect
- MeSH terms
- Aged, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Exudates and Transudates, Humans, Immunohistochemistry, Phosphorylation, Serine Endopeptidases, Skin, Wound Healing, Blotting, Western, Signal Transduction, Keratinocytes, Hepatocyte Growth Factor, Proto-Oncogene Proteins c-met
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
