title: Depletion of thymosin β4 promotes the proliferation, migration, and activation of human hepatic stellate cells.
abstract: OBJECTIVE
  It has recently been reported that thymosin beta-4 (Tβ4) 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 Tβ4 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 Tβ4 in serum, liver tissues, and LX-2 cells. Tβ4 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 Tβ4 was significantly reduced during the progression of liver fibrosis. The depletion of Tβ4 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 Tβ4 depletion in LX-2 cells can be counteracted by treatment with the Akt inhibitor MK-2206. In addition, Tβ4 depletion was also associated with the activation of HSCs via the enhanced expression of α-smooth muscle actin (α-SMA) and vimentin.
  
  
  CONCLUSIONS
  Our results suggest that Tβ4 participates in liver fibrosis by inhibiting the migration, proliferation, and activation of HSCs and that Tβ4 may be an effective target in the treatment of liver fibrosis.
authors: Department of Gastroenterology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors: Yongtao
authors: Y
authors: Xiao
authors: Chunying
authors: C
authors: Qu
authors: Wensong
authors: W
authors: Ge
authors: Baocan
authors: B
authors: Wang
authors: Jianxin
authors: J
authors: Wu
authors: Leiming
authors: L
authors: Xu
authors: Yingwei
authors: Y
authors: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D018450:Disease Progression; D055166:Hepatic Stellate Cells / Q000166:cytology*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013947:Thymosin / Q000235:genetics / Q000502:physiology*; D014746:Vimentin / Q000378:metabolism; D000099201:Thymosin beta(4)
chemical_list: D000199:Actins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D013947:Thymosin; D014746:Vimentin; D000099201:Thymosin beta(4); C541116:ACTA2 protein, human