β-arrestin2 deficiency protects against hepatic fibrosis in mice and prevents synthesis of extracellular matrix
Open Access
- 21 May 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (5), 1-15
- https://doi.org/10.1038/s41419-020-2596-8
Abstract
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.Keywords
Funding Information
- National Natural Science Foundation of China (81770605, 81300332)
- Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province (gxyqZD2018024)
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