Role of transmembrane protein 16A in vascular remodeling in portal hypertension induced by bile duct ligation of SD rats

Abstract

Objective To investigate the role of transmembrane protein 16A(TMEM16A)in murine portal vein remodeling in cirrhotic portal hypertension induced by bile duct ligation(BDL). Methods Sixty male SD rats were randomly divided into the model group(n= 40)and the control group(n= 20).Rats in the model group were subjected to BDL.Animals were sacrificed at 4th week.Hematoxylin and eosin(HE)staining was used to observe the liver cirrhosis in rats, and the portal vein pressure was measured to determine portal hypertension in rats.The change of histological structure of the portal vein was observed by HE staining.In addition, immunohistochemistry and Western blotting were applied to detect the expression of TMEM16A, phosphorylated extracellular signal- regulated kinase 1/2(p- ERK1/2)and extracellular signal - regulated kinase 1/2(ERK1/2) proteins. Results Compared with sham control group, the liver of rats in model group had false lobules and the portal vein pressure significantly increased[(16.79±2.65) mm Hg (1 mm Hg= 0.133 kPa)vs.(8.86±0.53)mm Hg,P<0.05].And the intima- media thickness of portal vein in model group was increased as compared with sham control group[(43.27±9.62)μm vs.(21.75±5.56) μm,P<0.05].The protein expression of TMEM16A was significantly decreased, and that of p- ERK1/2 was significantly increased in model group as compared with sham control group.The protein expression of ERK1/2 almost had no changes Conclusion TMEM16A may regulate the proliferation of portal vein smooth muscle cells by influencing the activity of mitogen- activated protein kinase(MAPK)/ERK signal pathway. Downregulation of TMEM16A may play an important role in the occurrence of portal vein remodeling induced by portal hypertension. Key words: Transmembrane protein 16A; Portal hypertension; Vascular remodeling; Cell proliferation; Mitogen-activated protein kinase/extracellular signal-regulated kinase signal pathway