Loss of MSP-dependent Ron receptor signaling exacerbates liver fibrosis in a high fat high cholesterol diet-induced ApoE KO mouse model
العنوان: | Loss of MSP-dependent Ron receptor signaling exacerbates liver fibrosis in a high fat high cholesterol diet-induced ApoE KO mouse model |
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المؤلفون: | Joselyn Natasha Allen, Mary Kennett, Andrew Patterson, Pamela A. Hankey-Giblin |
المصدر: | The Journal of Immunology. 200:42.26-42.26 |
بيانات النشر: | The American Association of Immunologists, 2018. |
سنة النشر: | 2018 |
مصطلحات موضوعية: | Immunology, Immunology and Allergy |
الوصف: | Liver fibrosis marks the turning point of non-alcoholic steatohepatitis and with no specific and effective anti-fibrotic therapies available, this disease is a major global health burden. Here, we established the novel role of the Ron receptor in mitigating liver fibrosis. For 18 weeks, apolipoprotein E (ApoE KO) and ApoE x Ron double knockout (DKO) mice were fed a fat and cholesterol-rich diet. Livers from DKO animals exhibited increased accumulation of sirius red-stained collagen. Immunohistochemistry of αSMA revealed that DKO livers had increased activation of collagen-producing hepatic stellate cells. In agreement with this, DKO livers exhibited higher expression of pro-fibrogenic molecules, PDGF, CTGF, and TGFβ. Additionally, DKO mice exhibited increased hepatic expression of collagens (Types 1, 3, and 4) and ECM remodeling proteins (MMP-2 and TIMP-1). The expression of pro-fibrogenic inflammatory cytokines (TNFα and IL-12b), receptors (TLR-4), and chemokines (MIP-2, CCL2, and CCL5) were significantly higher in DKO livers. DKO livers also exhibited increased infiltration of F4/80+ Kupffer cells, which are well-known to mediate the majority of cytokine and chemokine expression in fibrotic livers. Ron also attenuated several risk factors of liver fibrosis including insulin resistance, steatosis, hepatocellular damage, and inflammation. Despite lifestyle changes and pharmacotherapies for treating etiologies of liver fibrosis, the disrupted liver homeostasis often remains and requires effective treatments. Investigating the protective functions of Ron offers a pharmacological target for resolving the steatohepatitis spectrum. |
تدمد: | 1550-6606 0022-1767 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c06dec29a44b1652411dbe3d6d57b40e https://doi.org/10.4049/jimmunol.200.supp.42.26 |
رقم الأكسشن: | edsair.doi...........c06dec29a44b1652411dbe3d6d57b40e |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15506606 00221767 |
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