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 TGF β/Smad signalling pathway as a Smad3/4 adaptor protein. Aim 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 si RNA 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 pA kt 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.