title: β-2 spectrin is involved in hepatocyte proliferation through the interaction of TGFβ/Smad and PI3K/AKT signalling.
abstract: BACKGROUND
  Transforming growth factor (TGF) β signalling pathway plays a crucial role in liver regeneration following partial hepatectomy in mice. Evidence demonstrated that β-2 Spectrin is involved in TGFβ/Smad signalling pathway as a Smad3/4 adaptor protein.
  
  
  OBJECTIVE
  The aim of this study was to explore the role of β-2 Spectrin in hepatocyte proliferation.
  
  
  METHODS
  β-2 Spectrin expression was evaluated in mice receiving partial hepatectomy. The effect of siRNA against β-2 Spectrin on hepatocyte proliferation was determined. The interaction between TGFβ/Smad and PI3K/Akt signalling was investigated.
  
  
  RESULTS
  Hepatic β-2 Spectrin decreased dramatically 2 days after 70% hepatectomy in mice. In AML-12 cells, hepatocyte proliferation was inhibited after the stimulation of TGF β1 and a reduction in β-2 Spectrin mediated by siRNA resulted in increase in proliferative response. Confocal results revealed that β-2 Spectrin represented a key regulator in TGFβ/Smad signalling through controlling Smad3/4 subcellular localization. Moreover, Alternation of Akt phosphorylation led to the change in subcellular localization of Smad2, 3, 4 and β-2 Spectrin, A reduction in Smad2, 3 and 4 mediated by siRNA resulted in the induction of pAkt expression.
  
  
  CONCLUSIONS
  These findings reveal that β-2 Spectrin plays a crucial role in hepatocyte proliferation, which contributes to liver regeneration following hepatectomy in mice. In addition, PI3K/Akt is involved in TGFβ/Smad signalling pathway through the interaction with Smad proteins and β-2 Spectrin.
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Song
authors.forename: Wei
authors.initials: W
authors.lastname: Tu
authors.forename: Xingxing
authors.initials: X
authors.lastname: He
authors.forename: Jusheng
authors.initials: J
authors.lastname: Lin
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D008115:Liver Regeneration; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D013049:Spectrin
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; D013049:Spectrin; C497783:Smad2 protein, mouse; C497791:Smad3 protein, mouse; C490810:Smad4 protein, mouse