Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture.
Open accessAbstract
A consistent response to liver injury is the activation of resident mesenchymal cells known as lipocytes (Ito, fat-storing cells) into a proliferating cell type. In cultured lipocytes, platelet-derived growth factor (PDGF) is the most potent proliferative cytokine, but requires the activation-dependent expression of its receptor protein (Friedman, S. L., and M. J. P. Arthur. 1989. J. Clin. Invest. 84:1780-1785); the role of PDGF receptor (PDGFR) in liver injury is unknown. We have examined PDGFR gene expression in freshly isolated lipocytes during liver injury and correlated these findings with a culture model of cellular activation. Whereas lipocytes from normal rats had no detectable transcript for the beta-PDGFR subunit, this mRNA was induced within 1 h after a dose of carbon tetrachloride (CCl4). In contrast, alpha subunit mRNA was detected in normal cells, but was unchanged after liver injury. Similar results were observed in lipocytes from bile duct-obstructed rats, although beta-PDGFR induction was less marked. By immunoblot, induction of beta-PDGFR protein in lipocytes isolated from CCl4-treated animals correlated with mRNA increases. In contrast to lipocytes, endothelial cells from normal liver expressed low levels of alpha- and beta-receptor subunit mRNA, which did not increase with injury. Using a beta-PDGFR antibody, receptor protein could be identified within fibrotic septa in CCl4-treated animals in regions where cells expressed proliferating cell nuclear antigen (PCNA). In cultured lipocytes activated by growth on uncoated plastic, beta-PDGFR transcripts appeared within 3 d after plating, which coincided with the onset of cellular proliferation. In contrast, quiescent cells in suspension culture had no detectable beta-PDGFR mRNA. These results indicate that beta-PDGF receptor induction by lipocytes is an early event during hepatic injury in vivo and in primary culture.
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?
Other macrophage-secreted cytokines that may promote HSC activation include PDGF, TNFα, and IL-1β.
“Other macrophage-secreted cytokines that may promote HSC activation include PDGF, tumor necrosis factor alpha (TNFα), and interleukin 1 beta ( IL-1β) (65-69).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [67]
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
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
The Cellular Basis of Hepatic Fibrosis -- Mechanisms and Treatment Strategies
Flier, J. S., Underhill, L. H., & Friedman, S. L. (1993) · New England Journal of Medicine · doi:10.1056/nejm199306243282508 · Cited by 1,433 · see citing works
Self-citationNucleotide sequence of bacteriophage λ DNA
Sanger, F., Coulson, A. R., Hong, G. F., Hill, D. F., & Petersen, G. B. (1982) · Journal of Molecular Biology · doi:10.1016/0022-2836(82)90546-0 · Cited by 1,174 · see citing works
Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat.
Kountouras, J., Billing, B. H., & Scheuer, P. J. (1984) · PubMed · Cited by 679 · see citing works
Two Different Subunits Associate to Create Isoform-Specific Platelet-derived Growth Factor Receptors
Seifert, R. A., Hart, C. E., Phillips, P. E., Forstrom, J. W., Ross, R., Murray, M. J., & Bowen‐Pope, D. F. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81860-9 · Cited by 610 · see citing works
Pinzani, M., Gesualdo, L., Sabbah, G. M., & Abboud, H. E. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114363 · Cited by 477 · see citing works
PDGF ligand and receptor gene expression during repair of arterial injury.
Majesky, M. W., Reidy, M. A., Bowen‐Pope, D. F., Hart, C. E., Wilcox, J. N., & Schwartz, S. M. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.5.2149 · Cited by 429 · see citing works
Maher, J. J., & McGuire, R. F. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114886 · Cited by 426 · see citing works
Friedman, S. L., & Arthur, M. J. P. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114362 · Cited by 404 · see citing works
Self-citationFriedman, S. L., & Roll, F. J. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90673-7 · Cited by 361 · see citing works
Self-citationFriedman, S. L., Roll, F. J., Boyles, J. K., Arenson, D. M., & Bissell, D. M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)81686-6 · Cited by 354 · see citing works
Self-citationRat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture.
Rockey, D. C., Boyles, J. K., Gabbiani, G., & Friedman, S. L. (1992) · PubMed · Cited by 342 · see citing works
Self-citationGronwald, R. G., Grant, F. J., Haldeman, B. A., Hart, C. E., O’Hara, P. J., Hagen, F. S., Ross, R., Bowen‐Pope, D. F., & Murray, M. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.10.3435 · Cited by 316 · see citing works
Iida, H., Seifert, R. A., Alpers, C. E., et al. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.15.6560 · Cited by 294 · see citing works
High Yield Micronodular Cirrhosis in the Rat
Proctor, E., & Chatamra, K. (1982) · Gastroenterology · doi:10.1016/s0016-5085(82)80126-1 · Cited by 286 · see citing works
Ramadori, G. P., Veit, T., Schwögler, S., Dienes, H. P., Knittel, T. E., Rieder, H., & Büschenfelde, K. H. M. Z. (1990) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02899424 · Cited by 277 · see citing works
Milani, S., Herbst, H., Schuppan, D., Hahn, E. G., & Stein, H. (1989) · Hepatology · doi:10.1002/hep.1840100117 · Cited by 276 · see citing works
Perisinusoidal fat-storing cells are the main vitamin A storage sites in rat liver
Hendriks, H., Verhoofstad, W. A. M. M., Brouwer, A., Leeuw, A. M. D., & Knook, D. L. (1985) · Experimental Cell Research · doi:10.1016/0014-4827(85)90243-5 · Cited by 262 · see citing works
Carbon Tetrachloride Hepatotoxicity: An Example of Free Radical-Mediated Injury
Williams, A., & Burk, R. F. (1990) · Seminars in Liver Disease · doi:10.1055/s-2008-1040483 · Cited by 231 · see citing works
Geerts, A. E., Lazou, J.-M., Bleser, P. D., & Wisse, E. (1991) · Hepatology · doi:10.1002/hep.1840130628 · Cited by 203 · see citing works
The Role of Fat-Storing Cells in Disse Space Fibrogenesis in Alcoholic Liver Disease
MINATO, Y., Hasumura, Y., & Takeuchi, J. (1983) · Hepatology · doi:10.1002/hep.1840030414 · Cited by 178 · see citing works
Matsuoka, M., Pham, N., & Tsukamoto, H. (1989) · Liver International · doi:10.1111/j.1600-0676.1989.tb00382.x · Cited by 175 · see citing works
Friedman, S. L., Yamasaki, G., & Wong, L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34095-4 · Cited by 152 · see citing works
Self-citationPlatelet-derived growth factor receptors in the kidney—Upregulated expression in inflammation
Fellström, B., Klareskog, L., Heldin, C. H., et al. (1989) · Kidney International · doi:10.1038/ki.1989.306 · Cited by 143 · see citing works
In vivo responses of macrophages and perisinusoidal cells to cholestatic liver injury.
Je, H., Sj, J., & Burt, A. D. (1993) · PubMed · Cited by 137 · see citing works
Terracio, L., Rönnstrand, L., Tingström, A., et al. (1988) · The Journal of Cell Biology · doi:10.1083/jcb.107.5.1947 · Cited by 135 · see citing works
Expression of platelet-derived growth factor in a model of acute liver injury†
Pinzani, M., Milani, S., Grappone, C., Weber, F. L., Geñtilini, P., & Abboud, H. E. (1994) · Hepatology · doi:10.1002/hep.1840190323 · Cited by 131 · see citing works
Primary structure of human ribosomal protein S14 and the gene that encodes it.
Rhoads, D. D., Dixit, A., & Roufa, D. J. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.8.2774 · Cited by 131 · see citing works
Reuterdahl, C., Sundberg, C., Rubin, K., et al. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116429 · Cited by 117 · see citing works
Macrophage and perisinusoidal cell kinetics in acute liver injury
Johnson, S. J., Hines, J. E., & Burt, A. D. (1992) · The Journal of Pathology · doi:10.1002/path.1711660406 · Cited by 111 · see citing works
Mitogenic signals for platelet-derived growth factor isoforms in liver fat-storing cells
Pinzani, M., Knauss, T. C., Pierce, G. F., Hsieh, P., Kenney, W. C., Dubyak, G., & Abboud, H. E. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.260.3.c485 · Cited by 108 · see citing works
Two peptides related to platelet-derived growth factor are present in human wound fluid.
Matsuoka, J., & Grotendorst, G. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.12.4416 · Cited by 88 · see citing works
Bachem, M. G., Riess, U., & Gressner, A. M. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)92368-1 · Cited by 78 · see citing works
The role of fat-storing cells in Disse space fibrogenesis in alcoholic liver disease
志仁, 湊. (1983) · Medical Entomology and Zoology · Cited by 78 · see citing works
Lee, K. H., Bowen‐Pope, D. F., & Reed, R. R. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.2237 · Cited by 69 · see citing works
A homologue of platelet‐derived growth factor produced by rat alveolar macrophages
Kumar, R. K., Bennett, R. A. O., & Brody, A. R. (1988) · The FASEB Journal · doi:10.1096/fasebj.2.7.3280379 · Cited by 67 · see citing works
Early alcoholic liver injury: changes of the Disse space in acinar zone 3
Horn, T. D., Junge, J., & Christoffersen, P. (1985) · Liver International · doi:10.1111/j.1600-0676.1985.tb00253.x · Cited by 64 · see citing works
Davis, B. H., Rapp, U. R., & Davidson, N. O. (1991) · Biochemical Journal · doi:10.1042/bj2780043 · Cited by 59 · see citing works
Heldin, P., Pertoft, H., Nordlinder, H., Heldin, C., & Laurent, T. C. (1991) · Experimental Cell Research · doi:10.1016/0014-4827(91)90108-7 · Cited by 57 · see citing works
Geerts, A. E., Schellinck, P., Bouwens, L., et al. (1988) · Journal of Hepatology · doi:10.1016/s0168-8278(88)80461-6 · Cited by 54 · see citing works
Immunohistochemical detection of proliferating lipocytes in regenerating rat liver
Tanaka, Y., Mak, K. M., & Lieber, C. S. (1990) · The Journal of Pathology · doi:10.1002/path.1711600206 · Cited by 53 · see citing works
Primary Structure of Human Ribosomal Protein S14 and the Gene That Encodes It
Rhoads, D. D., Dixit, A., & Roufa, D. J. (1986) · Molecular and Cellular Biology · doi:10.1128/mcb.6.8.2774-2783.1986 · Cited by 48 · see citing works
Importance of PDGF receptor expression in accelerated atherosclerosis-chronic rejection.
Fellström, B., Dimény, E., Larsson, E., et al. (1989) · PubMed · Cited by 31 · see citing works
Isolation and Culture of Hepatic Nonparenchymal Cells
Friedman, S. L. (1993) · Elsevier eBooks · doi:10.1016/b978-0-12-461201-3.50032-3 · Cited by 21 · see citing works
Self-citationLee, K., Bowen‐Pope, D. F., & Reed, R. R. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.5.2237-2246.1990 · Cited by 13 · see citing works
Grundy, P., Bishayee, S., Disa, S., et al. (1989) · PubMed · Cited by 2 · see citing works
Subtraction cloning of lipocyte activating genes
FRIEDMAN, S. (1993) · Hepatology · doi:10.1016/0270-9139(93)91955-r · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver
Friedman, S. L. (2008) · Physiological Reviews · doi:10.1152/physrev.00013.2007 · Cited by 2,842 · see citing works
Self-citationLiver fibrosis – from bench to bedside
Friedman, S. L. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(02)00429-4 · Cited by 1,780 · see citing works
Self-citationHenderson, N. C., Arnold, T. D., Katamura, Y., Giacomini, M. M., Rodriguez, J. D., McCarty, J. H., Pellicoro, A., Raschperger, E., Betsholtz, C., Ruminski, P. G., et al. (2013) · Nature Medicine · doi:10.1038/nm.3282 · Cited by 866 · see citing works
Hepatic inflammatory responses in liver fibrosis
Hammerich, L., & Tacke, F. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00807-x · Cited by 803 · see citing works
Regulation of PDGF and its receptors in fibrotic diseases
Bonner, J. C. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2004.03.006 · Cited by 768 · see citing works
Therapy for Fibrotic Diseases: Nearing the Starting Line
Friedman, S. L., Sheppard, D., Duffield, J. S., & Violette, S. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004700 · Cited by 655 · see citing works
Self-citationPeroxisome proliferator-activated receptors and hepatic stellate cell activation
Miyahara, T., Schrum, L., Rippe, R., Xiong, S., Yee, H. F., Motomura, K., Anania, F. A., Willson, T. M., & Tsukamoto, H. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006577200 · Cited by 473 · see citing works
Hepatic fibrosis 2022: Unmet needs and a blueprint for the future
Friedman, S. L., & Pinzani, M. (2022) · Hepatology · doi:10.1002/hep.32285 · Cited by 430 · see citing works
Self-citationThe role of TGFβ1 in initiating hepatic stellate cell activation in vivo
Hellerbrand, C., Stefanovic, B., Giordano, F., Burchardt, E. R., & Brenner, D. A. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80010-5 · Cited by 393 · see citing works
Olaso, E., Labrador, J.-P., Wang, L., Ikeda, K., Eng, F. J., Klein, R., Lovett, D. H., Lin, H. C., & Friedman, S. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107571200 · Cited by 238 · see citing works
Self-citationBRD4 is a novel therapeutic target for liver fibrosis
Ding, N., Hah, N., Yu, R. T., Sherman, M. H., Benner, C., Leblanc, M., He, M., Liddle, C., Downes, M., & Evans, R. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522163112 · Cited by 211 · see citing works
Galli, A., Crabb, D., Price, D., Ceni, E., Salzano, R., Surrenti, C., & Casini, A. (2000) · Hepatology · doi:10.1002/hep.510310117 · Cited by 197 · see citing works
Rivera, C. A., Bradford, B. U., Hunt, K. J., Adachi, Y., Schrum, L. W., Koop, D. R., Burchardt, E.-R., Rippe, R. A., & Thurman, R. G. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.281.1.g200 · Cited by 165 · see citing works
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Wang, S., & Friedman, S. L. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0759 · Cited by 158 · see citing works
Self-citationGrappone, C., Pinzani, M., Parola, M., Pellegrini, G., Caligiuri, A., DeFranco, R., Marra, F., Herbst, H., Alpini, G., & Milani, S. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80169-x · Cited by 133 · see citing works
Radaeva, S., Wang, L., Radaev, S., Jeong, W.-I., Park, O., & Gao, B. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00212.2007 · Cited by 123 · see citing works
Hepatic Fibrosis, Stellate Cells, and Portal Hypertension
Rockey, D. C. (2006) · Clinics in Liver Disease · doi:10.1016/j.cld.2006.08.017 · Cited by 112 · see citing works
Hepatic Stellate Cells and Liver Fibrosis
Puche, J. E., Saiman, Y., & Friedman, S. L. (2013) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2013.tb00529.x · Cited by 89 · see citing works
Self-citationPrecision-cut human liver slice cultures as an immunological platform
Wu, X., Roberto, J. B., Knupp, A., Kenerson, H. L., Truong, C. D., Yuen, S. Y., Brempelis, K. J., Tuefferd, M., Chen, A., Horton, H., et al. (2018) · Journal of Immunological Methods · doi:10.1016/j.jim.2018.01.012 · Cited by 81 · see citing works
Hepatic Stellate Cells: Dictating Outcome in Nonalcoholic Fatty Liver Disease
Wiering, L., Subramanian, P., & Hammerich, L. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.02.010 · Cited by 80 · see citing works
GATA4 induces liver fibrosis regression by deactivating hepatic stellate cells
Arroyo, N., Villamayor, L., Díaz, I., Carmona, R., Ramos-Rodríguez, M., Muñoz-Chápuli, R., Pasquali, L., Toscano, M. G., Martín, F., Cano, D. A., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.150059 · Cited by 60 · see citing works
Activation of Platelet-Derived Growth Factor Receptor Alpha Contributes to Liver Fibrosis
Hayes, B. J., Riehle, K. J., Shimizu-Albergine, M., Bauer, R. L., Hudkins, K. L., Johansson, F., Yeh, M. M., Mahoney, W. M., Yeung, R. S., & Campbell, J. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092925 · Cited by 59 · see citing works
- Authors
- Wong, L., Yamasaki, G., Johnson, R. J., & Friedman, S. L.
- Affiliations
- San Francisco General Hospital (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1994-10-01
- Volume
- 94
- Issue
- 4
- Pages
- 1563-1569
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC295310
- OpenAlex
- W2155815716
- Cited by
- 304
- References
- 49
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 11 · 2022: 2 · 2021: 17 · 2020: 5 · 2019: 11 · 2018: 10 · 2017: 11 · 2016: 6 · 2015: 18 · 2014: 17 · 2013: 10 · 2012: 7
- FWCI
- 4.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- University of Washington
- National Institutes of Health (2p30am026743-06)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 43422, DK37340, R01DK037340)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- PDGFR, hepatic stellate cells, liver injury, carbon tetrachloride, biliary obstruction, liver fibrosis, cell activation, cell proliferation, endothelial cells
- MeSH terms
- Animals, Base Sequence, Cell Division, Cells, Cultured, Common Bile Duct, Constriction, Pathologic, Endothelium, Fibrosis, Gene Expression Regulation, Liver, Molecular Sequence Data, RNA, Messenger, Rats, Sprague-Dawley, Receptors, Platelet-Derived Growth Factor, Adipocytes, 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
