β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix
| Autor: | Yang Ma, Wu-Yi Sun, Yuan-Jing Gu, Jia-Jia Du, Jia-Chang Sun, Jingyu Chen, Wei Wei, Qingtong Wang, Xin-Ran Li |
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| Rok vydání: | 2019 |
| Předmět: |
Liver Cirrhosis
Male Cancer Research Immunology Down-Regulation Protective Agents Article Extracellular matrix Transforming Growth Factor beta1 Cellular and Molecular Neuroscience Treatment targets Medical research Hepatic Stellate Cells Animals lcsh:QH573-671 Rats Wistar Protein kinase B Cells Cultured Gastrointestinal diseases Chemistry lcsh:Cytology Cell Biology beta-Arrestin 2 In vitro β arrestin2 Extracellular Matrix Liver Hepatic stellate cell Cancer research Signal transduction Hepatic fibrosis |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 11, Iss 5, Pp 1-15 (2020) |
| ISSN: | 2041-4889 |
| Popis: | Hepatic fibrosis is a disease of the wound-healing response following chronic liver injury, and activated hepatic stellate cells (HSCs) play a crucial role in the progression of hepatic fibrosis. β-arrestin2 functions as a multiprotein scaffold to coordinate complex signal transduction networks. Although β-arrestin2 transduces diverse signals in cells, little is known about its involvement in the regulation of liver fibrosis. Our current study utilized a porcine serum-induced liver fibrosis model and found increased expression of β-arrestin2 in hepatic tissues with the progression of hepatic fibrosis, which was positively correlated with collagen levels. Furthermore, changes in human fibrotic samples were also observed. We next used β-arrestin2−/− mice to demonstrate that β-arrestin2 deficiency ameliorates CCl4-induced liver fibrosis and decreases collagen deposition. The in vitro depletion and overexpression experiments showed that decreased β-arrestin2 inhibited HSCs collagen production and elevated TβRIII expression, thus downregulating the TGF-β1 pathway components Smad2, Smad3 and Akt. These findings suggest that β-arrestin2 deficiency ameliorates liver fibrosis in mice, and β-arrestin2 may be a potential treatment target in hepatic fibrosis. |
| Databáze: | OpenAIRE |
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