ArticleFibrogenesis & tissue repair2014
Anaphylatoxin C5a modulates hepatic stellate cell migration.
Article in Fibrogenesis & tissue repair, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Non-transcriptional activity of IRF3 promotes liver fibrosis and stress granule assembly via a dsRNA-TLR3-dependent pathway in hepatic stellate cells.Hepatology (Baltimore, Md.) · 2026Article
- Investigating the role of Wnt3a and Wnt5a as critical factors of hepatic stellate cell activation in acute toxicant-induced liver injury.Cell biology and toxicology · 2024Article
- Role of Complement in Liver Diseases.Seminars in liver disease · 2024Review
- Recent Advances in Understanding of Pathogenesis of Alcohol-Associated Liver Disease.Annual review of pathology · 2023Review
- Role of G Protein-Coupled Receptors in Hepatic Stellate Cells and Approaches to Anti-Fibrotic Treatment of Non-Alcoholic Fatty Liver Disease.Frontiers in endocrinology · 2021Review
- Growth hormone induces Notch1 signaling in podocytes and contributes to proteinuria in diabetic nephropathy.The Journal of biological chemistry · 2019Article
- C5aR1 regulates migration of suppressive myeloid cells required for costimulatory blockade-induced murine allograft survival.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Complement 5a Receptor deficiency does not influence adverse cardiac remodeling after pressure-overload in mice.Scientific reports · 2017Article
- Contribution of the anaphylatoxin receptors, C3aR and C5aR, to the pathogenesis of pulmonary fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Soluble IgM links apoptosis to complement activation in early alcoholic liver disease in mice.Molecular immunology · 2016Article
- Targeting Extracellular Cyclophilins Ameliorates Disease Progression in Experimental Biliary Atresia.Molecular medicine (Cambridge, Mass.) · 2015Article
- The Role of Innate Immunity in Alcoholic Liver Disease.Alcohol research : current reviews · 2015Review
- Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology.Hepatobiliary surgery and nutrition · 2014Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundC5a and its cognate receptor, C5a receptor (C5aR), key elements of complement, are critical modulators of liver immunity and fibrosis. However, the molecular mechanism for the cross talk between complement and liver fibrosis is not well understood. C5a is a potent chemokine regulating migration of cells in the innate immune system. Since activation and migration of hepatic stellate cells (HSC) are hallmarks of liver fibrosis, we hypothesized that C5a contributes to fibrosis by regulating HSC activation and/or migration.
resultsPrimary cultures of mouse HSC increased expression of alpha smooth muscle actin (α-SMA) and collagen 1A (Col1A1) mRNA in response to activation on plastic. Expression of mRNA for C5aR, but not C5L2, a second C5a receptor that acts as a negative regulator, increased in parallel with markers of HSC activation in culture. Increased expression of C5aR on activated HSC was confirmed by immunocytochemistry. Cell surface expression of C5aR was also detected by flow cytometry on activated HSC isolated from mice expressing GFP under the control of the collagen promoter after exposure to chronic carbon tetrachloride. To understand the functional significance of C5aR expression in HSC, we next investigated whether C5a influenced HSC activation and/or migration. Challenge of HSC with C5a during culture had no effect on expression of α-SMA and Col1A1, suggesting that C5a did not influence HSC activation. Another important characteristic of HSC is their migratory capacity; migration of HSC in response to platelet derived growth factor (PDGF) and monocyte chemoattractant protein-1 (MCP-1) has been well characterized. Challenge of HSC with C5a enhanced HSC migration almost as efficiently as PDGF in a two-dimensional wound healing and Boyden chamber migration assays. C5a also stimulated expression of MCP-1. C5a-induced cell migration was slowed, but not completely inhibited, in presence of 227016, a MCP-1 receptor antagonist, suggesting C5a-induced migration occurs via both MCP-1-dependent and -independent mechanisms.
conclusionsThese data reveal that C5a regulates migration of HSC and suggest a novel mechanism by which complement contributes to hepatic fibrosis. C5a and its receptors are therefore potential therapeutic targets for the prevention and/or treatment of liver fibrosis.
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