Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells
Open accessAbstract
Background & aims Human hepatic stellate cells (HSCs), liver-specific pericytes, are currently considered major producers of extracellular matrix (ECM) components and key elements in the development of liver fibrogenesis. However, little is known about the possible functional interactions between HSCs and the various ECM components. Therefore, the present study was designed to evaluate the expression of integrins, the major family of extracellular matrix receptors. Methods Integrin expression was evaluated by immunoprecipitation and confirmed by immunocytochemistry and flow cytometry. Results Human HSCs were shown to express alpha1beta1, alpha2beta1, alpha(v)beta1. Adhesion to type IV collagen, type I collagen, fibronectin, and laminin 1 was inhibited by anti-beta1 antibody identifying beta1-containing integrins as possible receptors for these components. In addition, we showed that HSCs express alpha6beta4, a heterodimer known to mediate adhesion of epithelial cells to laminin and not previously characterized in mesenchymal cells. Adhesion to laminin 1 was not inhibited by antibodies specific for alpha6 or beta4, thus establishing that laminin 1 is not a ligand for alpha6beta4 in this cell type. Conclusions These findings represent the first description of integrin receptors in HSC and provide an attempt to cover the gap of information in the field of HSC-ECM interactions.
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?
aHSCs are the major producers of ECM components, which are key elements in liver fibrogenesis.
“aHSCs are known to be the major producers of ECM components, which are key elements in liver fibrogenesis [20].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [20]
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
No references could be resolved yet.
Research works printed but not linked: 29
- Lee EC, Lotz MM, Steele GD, Mercurio AM. The integrin a6b4 is tors expressed by human HSCs. The information reported a laminin receptor. J Cell Biol 1992;117:671-678. here constitutes the basis for further studies investigating
- Sonnenberg A, Linders CJT, Daams JH, Kennel SJ. The a6b1 the regulation of these receptors, the intracellular signal- (VLA-6) and a6b4 protein complexes: tissue distributions and biochemical properties. J Cell Sci 1990;96:207-217. ing events arising from their activation, and ultimately 19. Hemler ME, Crouse C, Sonnenberg A. Association of the VLA the biological outcome of these events. According to the a6 subunit with a novel protein. J Biol Chem 1989;264:6529- key role played by this cell type in liver ECM production 6535.
- Bodary SC, McLean JW. The integrin b1 subunit associates with and remodeling, these studies may greatly improve our the vitronectin receptor av subunit to form a novel vitronectin knowledge of the biology of this cell type, and particu- receptor in a human embryonic kidney cell line. J Biol Chem larly of their role in liver fibrogenesis. 1990;265:5938-5941.
- Spinardi L, Ren Y-L, Sanders R, Giancotti FG. The b4 subunit References cytoplasmic domain mediates the interaction of a6b4 integrin with the cytoskeleton of hemidesmosomes. Mol Biol Cell 1. Maher JJ, McGuire RF. Extracellular matrix gene expression in- 1993;4:871-884. creases preferentially in rat lipocytes and sinusoidal endothelial 22. Wake K. Liver perivascular cells revealed by gold-and silver- cells during hepatic fibrosis in vivo. J Clin Invest 1990;86:1641- impregnation methods and electron microscopy. In: Motta PM, 1648. ed. Biopathology of the liver: an ultrastructural approach. Dor- 2.
- Maher JJ, Friedman SL, Roll FJ, Bissell DM. Immunolocalization of drecht, The Netherlands: Kluwer, 1988:23-36. laminin in normal rat liver and biosynthesis of laminin by hepatic 23. Wake K. Perisinusoidal stellate cells (fat-storing cells, interstitial lipocytes in primary cultures. Gastroenterology 1988;94:1053- cells, lipocytes), their related structure in and around the liver 1062. sinusoids, and vitamin A-storing cells in extrahepatic organs.
- Ramadori G, Knittel T, Odenthal M, Schwogler S, Neubauer K, Int Rev Cytol 1980;66:303-353.
- Meyer Zum Buschenfelde KH. Synthesis of cellular fibronectin by 24. Ramadori G. The stellate cell (Ito cell, fat-storing cell, lipocyte, rat liver fat-storing (Ito) cells: regulation by cytokines. Gastroen- perisinusoidal cell) of the liver. New insights into pathophysiology terology 1992;103:1313-1321. of intriguing cell. Virchows Arch B Cell Pathol Incl Mol Pathol
- Reid ML, Fiorino AS, Sigal SH, Brill S, Holst PA. Extracellular 1991;61:147-158. matrix gradients in the space of Disse: relevance to liver biology.
- Knittel T, Schuppan D, Meyer Zum Buschenfelde K, Ramadori G. Hepatology 1992;15:1198-1203. Differential expression of collagen type I, III, and IV by fat-storing 5. Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267: (Ito) cell in vitro. Gastroenterology 1992;102:1724-1735. 10931-10934.
- Loreal O, Levavasseur F, Rescam P, Yamada Y, Guillouzo A, 6. Matsuoka M, Pham NT, Tsukamoto H. Differential effects of in- Clement B. Differential expression of laminin chain in hepatic terleukin-1 a, tumor necrosis factor a, and transforming growth lipocytes. FEBS Lett 1991;290:9-12. factor b1 on cell proliferation and collagen formation by cultured 27. Hall DE, Reichardt LF, Crowley E, Holley B, Moezzi H, Sonnenberg fat-storing cells. Liver 1989;9:71-78.
- A, Damsky CH. The a1b1 and a6b1 integrin heterodimers medi- 7. Ruoslahti E. Integrins. J Clin Invest 1991;87:1-5. ate cell attachment to distinct sites on laminin. J Cell Biol 8. Hynes RO. Integrins: versatility, modulation, and signaling in cell 1990;110:2175-2184. adhesion. Cell 1992;69:11-25.
- Ignatius MJ, Reichardt LF. Identification of a neuronal laminin 9. Juliano RL, Haskill S. Signal transduction from the extracellular receptor: an Mr 200/120 kD integrin heterodimer that binds matrix. J Cell Biol 1993;120:577-585. laminin in a divalent cation-dependent manner. Neuron
- Clark EA, Brugge JS. Integrins and signal transduction pathways: 1988;1:713-725. the road taken. Science 1995;268:233-239.
- Vandenberg P, Kern A, Ries A, Luckenbill-Edds L, Mann K, Kuhn 11. Couvelard A, Scoazec JY, Feldmann G. Expression of cell-cell and K. Characterization of a type IV collagen major cell binding site cell-matrix adhesion proteins by sinusoidal endothelial cells in with affinity to the a1b1 and the a2b1 integrins. J Cell Biol the normal and cirrhotic human liver. Am J Pathol 1991;113:1475-1483. 1993;143:738-752.
- Elices MJ, Hemler ME. The human integrin VLA-2 is a collagen 12. Volpes R, Van den Oord JJ, Desmet VJ. Distribution of the VLA receptor on some cells and a collagen/laminin receptor on oth- family of integrins in normal and pathological liver tissue. Gastro- ers. Proc Natl Acad Sci USA 1989;86:9906-9910. enterology 1991;101:200-206.
- Pinzani M, Failli P, Ruocco C, Casini A, Milani S, Baldi E, Giotti A, Gentilini P. Fat-storing cells as liver-specific pericytes: spatial ities. J Biol Chem 1990;265:615-618. dynamics of agonist-stimulated intracellular calcium transients. 32. Wayner EA, Orlando RA, Cheresh DA. Integrin avb3 and avb5 J Clin Invest 1992;90:642-646. contribute to cell attachment to vitronectin but differentially dis- tribute to the cell surface. J Cell Biol 1991;113:919-929.
- Casini A, Pinzani M, Milani S, Grappone C, Galli G, Jezequel AM, Schuppan D, Rotella CM, Surrenti C. Regulation of transforming 33. Hostikka SL, Tryggvason K. The complete primary structure of growth factor b1 in human fat-storing cells. Gastroenterology the a2 chain of human type IV collagen and comparison with 1993;105:245-253.
- a1(IV) chain. J Biol Chem 1988;263:19488-19493.
- Vogel BE, Tarone G, Giancotti FG, Gailit J, Ruoslahti E. A novel 15. Sonnenberg A, Janssen H, Hogervorst F, Calafat J, Hilgers J. A fibronectin receptor with an unexpected subunit composition complex of platelet glycoproteins Ic and IIa identified by a rat (avb1). J Biol Chem 1990;1265:5934-5937. monoclonal antibody. J Biol Chem 1987;262:10376-10383.
- Dedhar S, Gray V. Isolation of a novel integrin receptor mediating 16. Van Waes C, Kozarsky KF, Warren AB, Kidd L, Paugh D, Liebert ARG-GLY-ASP directed cell adhesion to fibronectin and type I col- M, Carey TE. The A9 antigen associated with aggressive human lagen from human neuroblastoma cells. Association of a novel squamous carcinoma is structurally and functionally similar to b1-related subunit with av. J Cell Biol 1990;110:2185-2193. the newly defined integrin a6b4. Cancer Res 1991;51:2395- 2402.
- Tawil N, Wilson P, Carbonetto S. Integrins in point contacts medi- / 5e0b$$0008 03-07-96 17:00:33 gasas WBS-Gastro ate cell spreading: factors that regulate integrin accumulation in M, Garrod D. Integrin a6/b4 complex is located in hemidesmo- somes, suggesting a major role in epidermal cell-basement mem- point contacts vs. focal contacts. J Cell Biol 1993;120:261- 271. brane adhesion. J Cell Biol 1991;113:907-917.
- Kennel SJ, Godfrey V, Chang LY, Lankford TK, Foote LJ, Makkinie 37. Nermut MV, Eason P, Hirst EM, Kellie S. Cell/substratum adhe- A. The beta 4 subunit of the integrin family is displayed on a sion in RSV-transformed rat fibroblasts. Exp Cell Res 1991; restricted subset of endothelium in mice. J Cell Sci 193:382-397. 1992;96:207-215.
- Singer II, Scout S, Kawka DW, Kazazis DM, Gailit J, Ruoslahti E. 47. Mechtersheimer G, Barth T, Hartschuh W, Lehnert T, Moller P. Cell surface distribution of fibronectin and vitronectin receptors In situ expression of b1, b3 and b4 integrin subunits in non- depends on substrate composition and extracellular matrix accu- neoplastic endothelium and vascular tumours. Virchows Arch mulation. J Cell Biol 1988;106:2171-2181. 1994;425:375-384.
- Lotz MM, Kornelius CA, Mercurio AM. Human colon carcinoma 48. Cremona O, Savoia P, Marchisio PC, Gabbiani G, Chaponnier C. cells use multiple receptors to adhere to laminin: involvement The a6 and b4 integrin subunits are expressed by smooth muscle of a6b4 and a2b1 integrins. Cell Regul 1990;1:249-257. cells of human small vessels: a new localization in mesenchymal 40. Mercurio AM. Laminin receptors: achieving specificity through cells. J Histochem Cytochem 1994;42:1221-1228. cooperation. Trends Cell Biol 1995;5:419-423.
- Kemperman H, Wijnands Y, De Rijk D, Roos E. The integrin alpha 41. Kennel SJ, Foote LJ, Falcioni R, Sonnenberg A, Stringer CD, 6 beta 4 on TA3/Ha mammary carcinoma cells is involved in Crouse C, Hemler ME. Analysis of the tumor associated antigen adhesion to hepatocytes. Cancer Res 1993;53:3611-3617.
- TSP-180. Identity with a6b4 in the integrin superfamily. J Biol Chem 1989;264:15515-15521.
- beta 4 integrin heterodimer is a component of hemidesmo- Address requests for reprints to: Vinicio Carloni, M.D., Ph.D., Isti- somes. Proc Natl Acad Sci USA 1990;87:8970-8974.
- tuto di Medicina Interna, Universita ´di Firenze, Viale Morgagni, 85, 43. Riddelle KS, Green KJ, Jones JCR. Formation of hemidesmo- I-50134 Firenze, Italy. Fax: (39) 55-417123. somes in vitro by a transformed bladder cell line. J Cell Biol Supported in part by grants from Ministero Italiano dellUniversita ´ 1991;112:159-168. e della Ricerca Scientifica e Tecnologica Progetto Nazionale Epatiti
- Spinardi L, Einheber S, Cullen T, Milner TA, Giancotti FG. A recom- Virali e Cirrosi Epatica, Rome, Italy. Financial support was also pro- binant tail-less b4 subunit disrupts hemidesmosomes, but does vided by Fondazione Italiana per lo Studio del Fegato, Italian Liver not suppress a6b4-mediated cell adhesion to laminins. J Cell Foundation, Florence, Italy. Biol 1995;129:473-487.
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
Acute Alcohol-Induced Liver Injury
Massey, V. L., & Arteel, G. E. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00193 · Cited by 147 · see citing works
Shao, M., Zhang, X., Sun, J., Dong, H., Han, X., Yang, Q., Chen, R., Shen, L., Xu, L., Wang, L., et al. (2025) · Exploration · doi:10.1002/exp.70000 · Cited by 26 · see citing works
- Authors
- Carloni, V, Romanelli, R., Pinzani, M., Laffi, G., & Gentilini, P.
- Affiliations
- University of Florence (IT)
- ORCID
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 1996-04
- Volume
- 110
- Issue
- 4
- Pages
- 1127-1136
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2111868375
- Cited by
- 113
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 4 · 2013: 1 · 2012: 3
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- hepatic stellate cells, integrins, collagen, laminin, alpha1beta1 integrin, alpha2beta1 integrin, alpha5beta1 integrin, alpha6beta4 integrin, extracellular matrix receptors, cell adhesion, liver fibrosis, extracellular matrix
- MeSH terms
- Cell Adhesion, Cells, Cultured, Collagen, Extracellular Matrix, Fibronectins, Humans, Immunohistochemistry, Laminin, Liver, Precipitin Tests, Integrins, Receptors, Laminin, Adipocytes, Receptors, Collagen
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