Overexpression of Activin βC or Activin βE in the Mouse Liver Inhibits Regenerative Deoxyribonucleic Acid Synthesis of Hepatic Cells
Abstract
Activins are dimeric growth factors composed of beta-subunits, four of which have been isolated so far. Whereas activin beta(A) and beta(B) are expressed in many tissues, the expression of activin beta(C) and beta(E) is confined to the liver. To date no biological role or activity has been assigned to activins formed from beta(C) or beta(E) subunits (activin C and E). Because activin A (beta(A)beta(A)), among its various functions in other tissues, appears to be a negative regulator of liver growth, we hypothesized a similar role for activin C and E. Using a nonviral gene transfer system we specifically delivered genes encoding activin beta(C), beta(E), or beta(A) to the mouse liver. The mRNA analysis and reporter gene coexpression both indicated a reproducible temporal and spatial transgene expression pattern. The effects of activin overexpression were studied in the context of a regenerative proliferation of hepatic cells, a result of the tissue damage associated with the hydrodynamics based gene transfer procedure. Activin beta(C), beta(E), or beta(A) expression, all temporarily inhibited regenerative DNA synthesis of hepatocytes and nonparenchymal cells, though to a varying degree. This first report of a biological activity of activin C and E supports an involvement in liver tissue homeostasis and further emphasizes the role of the growing activin family in liver physiology.
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?
Circulating levels of activin-E are elevated in high-fat diet-fed mice and are thought to contribute to resistance to body weight gain.
“Furthermore, circulating levels of activin-E are elevated in high-fat diet-fed mice and are thought to contribute to resistance to body weight gain [28,30].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [28]
Activin-E is expressed and secreted primarily by the liver, unlike other activins that are expressed throughout the body.
“Activin-E (also called inhibin subunit beta E) was recently identified in humans and rodents and, unlike other activins that are expressed throughout the body, activin-E is expressed and secreted primarily by the liver [27,28].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [28]
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
A simple, rapid, and sensitive DNA assay procedure
Labarca, C. G., & Paigen, K. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90165-7 · Cited by 4,905 · see citing works
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828 · see citing works
Lethal effect of the anti-Fas antibody in mice
Ogasawara, J., Watanabe-Fukunaga, R., Adachi, M., Matsuzawa, A., Kasugai, T., Kitamura, Y., Itoh, N., Suda, T., & Nagata, S. (1993) · Nature · doi:10.1038/364806a0 · Cited by 1,881 · see citing works
Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA
Liu, F., Song, Y. K., & Liu, D. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300947 · Cited by 1,728 · see citing works
Kraupp, B. G., Ruttkay-Nedecký, B., Koudelka, H., Bukowska, K., Bursch, W., & Schulte‐Hermann, R. (1995) · Hepatology · doi:10.1002/hep.1840210534 · Cited by 1,167 · see citing works
Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid
Vale, W., Rivier, J., Vaughan, J. M., McClintock, R. A., CORRIGAN, A. Z., WOO, W., Karr, D., & Spiess, J. (1986) · Nature · doi:10.1038/321776a0 · Cited by 1,155 · see citing works
Pituitary FSH is released by a heterodimer of the β-subunits from the two forms of inhibin
LING, N. C., Ying, S., Ueno, N., Shimasaki, S., Esch, F. S., Hotta, M., & Guillemin, R. (1986) · Nature · doi:10.1038/321779a0 · Cited by 1,082 · see citing works
Zhang, G., Budker, V. G., & Wolff, J. A. (1999) · Human Gene Therapy · doi:10.1089/10430349950017734 · Cited by 944 · see citing works
Genetic Analysis of the Mammalian Transforming Growth Factor-β Superfamily
Chang, H., Brown, C., & Matzuk, M. M. (2002) · Endocrine Reviews · doi:10.1210/er.2002-0003 · Cited by 779 · see citing works
The role of hepatocytes and oval cells in liver regeneration and repopulation
Fausto, N., & Campbell, J. S. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(02)00338-6 · Cited by 646 · see citing works
Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration.
Fausto, N., Laird, A., & Webber, E. M. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.15.8529831 · Cited by 620 · see citing works
Chapter 1 Anatomical Methods in Cell Death
Kerr, J. F. R., Gobe, G. C., Winterford, C. M., & HARMON, B. V. (1995) · Methods in cell biology · doi:10.1016/s0091-679x(08)61921-4 · Cited by 469 · see citing works
Russell, W. E., Coffey, R. J., Ouellette, A. J., & Moses, H. L. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.14.5126 · Cited by 427 · see citing works
Sabath, D. E., Broome, H. E., & Prystowsky, M. B. (1990) · Gene · doi:10.1016/0378-1119(90)90087-8 · Cited by 383 · see citing works
Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice.
Matzuk, M. M., Finegold, M. J., Mather, J. P., KRUMMEN, L. A., Lu, H., & Bradley, A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8817 · Cited by 374 · see citing works
Transforming growth factor β and the liver
Bissell, M. D., Roulot, D. M., & George, J. (2001) · Hepatology · doi:10.1053/jhep.2001.28457 · Cited by 348 · see citing works
The Cystine-Knot Growth-Factor Superfamily
Sun, P. D., & Davies, D. R. (1995) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.bb.24.060195.001413 · Cited by 285 · see citing works
Follistatin: A Multifunctional Regulatory Protein
Phillips, D. J., & de Kretser, D. M. (1998) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1998.0169 · Cited by 274 · see citing works
Woodruff, T. K., Meunier, H., Jones, P., et al. (1987) · Molecular Endocrinology · doi:10.1210/mend-1-8-561 · Cited by 211 · see citing works
Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes.
Yasuda, H., Mine, T., Shibata, H., Eto, Y., Hasegawa, Y., Takeuchi, T., Asano, S., & Kojima, I. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116727 · Cited by 204 · see citing works
Activin Signal Transduction Pathways
Pangas, S. A., & Woodruff, T. K. (2000) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(00)00294-0 · Cited by 200 · see citing works
Institute for Laboratory Animal Research
Zurlo, J. (2002) · doi:10.21236/ada400956 · Cited by 168 · see citing works
Cloning of a New Member of the TGF-β Family: A Putative New Activin βC Chain
Hötten, G., Neidhardt, H., Schneider, C., & Pohl, J. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1086 · Cited by 167 · see citing works
Jakowlew, S. B., Mead, J. E., Danielpour, D., Wu, J., Roberts, A. B., & Fausto, N. (1991) · Cell Regulation · doi:10.1091/mbc.2.7.535 · Cited by 147 · see citing works
Regulation of Cellular and System Function by Activin
Woodruff, T. K. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(97)00477-2 · Cited by 138 · see citing works
Activin B: Precursor Sequences, Genomic Structure andin VitroActivities
Mason, A. J., Berkemeier, L. M., Schmelzer, C. H., & SCHWALL, R. H. (1989) · Molecular Endocrinology · doi:10.1210/mend-3-9-1352 · Cited by 128 · see citing works
Activin βC and βE Genes Are Not Essential for Mouse Liver Growth, Differentiation, and Regeneration
Lau, A. L., Kumar, T. R., Nishimori, K., Bonadio, J. F., & Matzuk, M. M. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.16.6127-6137.2000 · Cited by 126 · see citing works
Molecular Cloning of the Mouse Activin βESubunit Gene
Fang, J., Yin, W., Smiley, E. C., Wang, S. Q., & Bonadio, J. F. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1715 · Cited by 125 · see citing works
Determinants of translational fidelity and efficiency in vertebrate mRNAs
Kozak, M. (1994) · Biochimie · doi:10.1016/0300-9084(94)90182-1 · Cited by 125 · see citing works
Hepatic oval ‘stem’ cell in liver regeneration
Oh, S., Hatch, H. M., & Petersen, B. E. (2002) · Seminars in Cell and Developmental Biology · doi:10.1016/s1084952102001271 · Cited by 117 · see citing works
Role of TGF-? in immune-evasion of cancer
Beck, C., Schreiber, H. W., & Rowley, D. A. (2001) · Microscopy Research and Technique · doi:10.1002/1097-0029(20010215)52:4 · Cited by 103 · see citing works
Yang, J., Chen, S., Huang, L., Michalopoulos, G. K., & Liu, Y. (2001) · Hepatology · doi:10.1053/jhep.2001.23438 · Cited by 102 · see citing works
Mellor, S. L., Cranfield, M., Ries, R., Pedersen, J., Cancilla, B., de Kretser, D., Groome, N. P., Mason, A. J., & Risbridger, G. P. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.12.7052 · Cited by 101 · see citing works
Kogure, K., Omata, W., Kanzaki, M., Zhang, Y.-Q., Yasuda, H., Mine, T., & Kojima, I. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90212-0 · Cited by 101 · see citing works
Inhibins, Activins, and Follistatins: The Saga Continues
DePaolo, L. V. (1997) · Experimental Biology and Medicine · doi:10.3181/00379727-214-44100 · Cited by 78 · see citing works
Fang, J., Wang, S., Smiley, E. C., & Bonadio, J. F. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6162 · Cited by 74 · see citing works
Kogure, K., Zhang, Y.-Q., Maeshima, A., Suzuki, K., Kuwano, H., & Kojima, I. (2000) · Hepatology · doi:10.1053/he.2000.6100 · Cited by 66 · see citing works
Vejda, S., Cranfield, M., Peter, B., Mellor, S. L., Groome, N. P., Schulte‐Hermann, R., & Rossmanith, W. (2002) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0280137 · Cited by 63 · see citing works
Self-citationSchmitt, J., Hötten, G., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Pohl, J., & Schrewe, H. (1996) · Genomics · doi:10.1006/geno.1996.0130 · Cited by 58 · see citing works
cDNA cloning and expression of human activin βE subunit
Hashimoto, O., Tsuchida, K., Ushiro, Y., Hosoi, Y., Hoshi, N., Sugino, H., & Hasegawa, Y. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00157-0 · Cited by 54 · see citing works
Rossmanith, W., Chabicovsky, M., Grasl‐Kraupp, B., Peter, B., Schausberger, E., & Schulte‐Hermann, R. (2002) · Molecular Carcinogenesis · doi:10.1002/mc.10068 · Cited by 39 · see citing works
Self-citationCloning and regulation of the rat activin betaE subunit
O’Bryan, M. K., Sebire, K., Gerdprasert, O., Hedger, M. P., Mt, H., & de Kretser, D. (2000) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0240409 · Cited by 39 · see citing works
Rossmanith, W., Chabicovsky, M., Herkner, K. R., et al. (2002) · DNA and Cell Biology · doi:10.1089/104454902320908496 · Cited by 38 · see citing works
Self-citationApoptosis and prognosis in cancer: rationale and relevance.
Langlois, N. E. I., Eremin, O., & Heys, S. (2000) · PubMed · Cited by 31 · see citing works
Niemuller, C., Randall, K. J., Webb, D. J., et al. (1995) · Endocrinology · doi:10.1210/endo.136.12.7588280 · Cited by 28 · see citing works
Kallenbach, M., No, R., & Schulte‐Hermann, R. (1983) · PubMed · Cited by 19 · see citing works
Expression of mouse RNase MRP RNA in human embryonic kidney 293 cells
Rossmanith, W., Bettinger, E., Cerni, C., et al. (1997) · Molecular Biology Reports · doi:10.1023/a:1006882704481 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Vejda S 2002 Characterization of activin C and E, two liver-specific members of the activin family. Vienna, Austria: University of Vienna; PhD thesis
- Popper H 1988 Hepatocellular degeneration and death. In: Arias IM, Jakoby WB, Popper H, Schachter D, Shafritz DA, eds. The liver. biology and patho- biology. New York: Raven Press; 1087-1103
Cited by
Sorted by citations
Hepatokines and metabolism: Deciphering communication from the liver
Jensen-Cody, S. O., & Potthoff, M. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101138 · Cited by 252 · see citing works
Roles of activin in tissue repair, fibrosis, and inflammatory disease
WERNER, S., & ALZHEIMER, C. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2006.01.001 · Cited by 209 · see citing works
Activin E controls energy homeostasis in both Brown and white adipose tissues as a hepatokine
Hashimoto, O., Funaba, M., Sekiyama, K., Doi, S., Shindo, D., Satoh, R., Itoi, H., Oiwa, H., Morita, M., Suzuki, C., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.10.008 · Cited by 77 · see citing works
A spatiotemporal atlas of mouse liver homeostasis and regeneration
Xu, J., Guo, P., Hao, S., Shangguan, S., Shi, Q., Volpe, G., Huang, K., Zuo, J., An, J., Yuan, Y., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01709-7 · Cited by 75 · see citing works
Sugiyama, M., Kikuchi, A., Misu, H., Igawa, H., Ashihara, M., Kushima, Y., Honda, K., Suzuki, Y., Kawabe, Y., Kaneko, S., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194798 · Cited by 52 · see citing works
- Authors
- Chabicovsky, M., Herkner, K., & Rossmanith, W.
- Affiliations
- University of Vienna (AT)
- Ludwig Boltzmann Institute for Pediatric Endocrinology and Immunology (K.H.), 1090 Vienna, Austria
- Corresponding author
- Rossmanith, Walter
- ORCID
- Rossmanith, Walter
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2003-08-01
- Volume
- 144
- Issue
- 8
- Pages
- 3497-3504
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2054684099
- Cited by
- 74
- References
- 47
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 1 · 2015: 3 · 2013: 1 · 2012: 2
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- activin, liver regeneration, hepatocyte proliferation, DNA synthesis, hydrodynamic gene transfer, transgene expression, non-parenchymal liver cells, growth factor overexpression
- MeSH terms
- Animals, DNA, Homeostasis, Liver, Liver Regeneration, Male, Mice, Inbred BALB C, RNA, Messenger, Transfection, Gene Expression, Inhibin-beta Subunits, Mice, Rats
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
