Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 34, Issue 2, Pages 356-367Publisher
KARGER
DOI: 10.1159/000363005
Keywords
Thymosin beta 4; Liver fibrosis; Hepatic stellate cell; Proliferation; Migration
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Funding
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition [11DZ2260500]
- Shanghai Committee of Science and Technology [11ZR1424000]
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Background & Aims: It has recently been reported that thymosin beta-4 (T beta 4) has anti-fibrogenic effects in human hepatic stellate cells (HSCs) in vitro, but the mechanisms underlying these effects remain unclear. The aim of this study was to investigate the roles of T beta 4 in the proliferation, migration, and activation of HSCs. Methods: Enzyme linked immunosorbent assays (ELISA), immunohistochemistry, and western blot assays were utilized to determine the expression levels of T beta 4 in serum, liver tissues, and LX-2 cells. T beta 4 was depleted in LX-2 cells using small interfering RNAs (siRNAs). Cell proliferation was analyzed using cell counting kit-8 (CCK-8) viability assays, and cell migration was investigated using wound healing and transwell migration assays. Results: The expression of T beta 4 was significantly reduced during the progression of liver fibrosis. The depletion of T beta 4 significantly promoted the proliferation and migration of LX-2 cells via the activation of the PI3K/Akt signaling pathway. The pro migratory and pro proliferative effects of T beta 4 depletion in LX-2 cells can be counteracted by treatment with the Akt inhibitor MK-2206. In addition, T beta 4 depletion was also associated with the activation of HSCs via the enhanced expression of alpha-smooth muscle actin (alpha-SMA) and vimentin. Conclusions: Our results suggest that T beta 4 participates in liver fibrosis by inhibiting the migration, proliferation, and activation of HSCs and that T beta 4 may be an effective target in the treatment of liver fibrosis. Copyright (C) 2014 S. Karger AG, Basel
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