Effects Of Notch Signaling In Rats With Hepatic Fibrosis

Objective:The occurrence and development of liver fibrosis is a complicated process, numerous cell signal pathways involved. Notch signaling pathway is a widespread signaling pathway, studies have confirmed Notch signaling pathways play an important role in renal fibrosis, pulmonary fibrosis,peritoneal fibrosis and other fibrosis, but the role of Notch signaling pathway in the liver fibrosis has not been reported. This experiment as the hepatic fibrosis induced by ccl4in rats as the research object, to investigate the effects of Notch signaling pathway in the progression of hepatic fibrosis, and then provide further evidence for cellular mechanism of hepatic fibrosis.Methods:Forty healthy wistar rats were randomly divided into2groups:control group (n=15) and liver fibrosis group (n=25). Experimental liver fibrosis was induced by subcutaneous injection of CC14.At the end of8weeks, histopathological study of liver tissue was done with hematoxylin-eosin (HE). Notch-1、E-cadherin and Transforming growth factor-β1(TGF-β1) in liver were examined with theimmunohisochemist-rical technique.Results:A significant collagen deposition、hepatocyte necrosis and rearrangement of the parenchyma were noted in liver tissue of liver fibrosis group. The expression levels of Notch-1(10.37±1.27vs2.72±1.11,P<0.01) and were TGF-β1(9.18±1.18vs1.95±1.09, P <0.01)were considerably increased in model group than those in control group. Contrarily, the expression levels of E-cadherin was increased considerably in the model animals (2.13±1.04vs9.69±1.67, P<0.01). Notch-1、TGF-β1were correlated with E-cadherin, and the correlation coefficients were-0.70(P<0.05)and-0.77(P<0.05)respectively, Notch-1was correlated with TGF-β1, and the correlation coefficients were0.78(P<0.05).And the expressions of Notch-1、TGF-β1and E-cadherin were closely correlated with the hepatic fibrosis stages (r=0.89、0.86、-0.79, respectively; P<0.05).Conclusion:The Notch-1may participate in the development and progression of hepatic fibrosis, and also closely correlated with the severity of liver fibrosis. The development and progression of hepatic fibrosis associated witch EMT, which accompanied by the E-cadherin missing.The Notch-1and TGF-β1have consistency in the development and progression of hepatic fibrosis, which via raising Snail gene to suppress E-cadherin and then start EMT, and promote the development of liver fibrosis.