Abstract
BackgroundHepatic stellate cells (HSCs) are one of the main cell types involved in liver fibrosis induced by many factors, including schistosomes. Previous studies in our lab have shown that recombinant P40 protein from Schistosoma japonicum (rSjP40) can inhibit HSC activation in vitro. Let-7b is a member of the let-7 microRNA family and plays an inhibitory role in a variety of diseases and inflammatory conditions. In this study, we investigated the role of let-7b in the inhibition of HSC activation by rSjP40.MethodsExpression of let-7b was detected by quantitative real-time PCR. A dual luciferase assay was used to confirm direct interaction between let-7b and collagen I. We also used western blot to assess protein levels of TGFβRI and collagen type I α1 (COL1A1).ResultsWe found that rSjP40 up-regulates expression of let-7b in HSCs. Let-7b inhibits collagen I expression by directly targeting the 3’UTR region of the collagen I gene. Furthermore, we discovered that let-7b inhibitor partially restores the loss of collagen I expression caused by rSjP40.ConclusionOur research clarifies the role of let-7b in the inhibition of HSC activation by rSjP40 and will provide new insights and ideas for the inhibition of HSC activation and treatment of liver fibrosis.
Highlights
Liver fibrosis is a response to chronic liver damage caused by various factors, such as schistosomiasis, viral hepatitis, alcoholism and cholestasis [1,2]
We found that recombinant SjP40 (rSjP40) up-regulates expression of let-7b in Hepatic stellate cells (HSCs)
We discovered that let-7b inhibitor partially restores the loss of collagen I expression caused by rSjP40
Summary
Liver fibrosis is a response to chronic liver damage caused by various factors, such as schistosomiasis, viral hepatitis, alcoholism and cholestasis [1,2]. Hepatic stellate cells (HSCs) are considered to be one of the main cell types involved in liver fibrosis [3]. Studies have shown that the eggs of both Schistosoma japonicum and Schistosoma mansoni can inhibit HSC activation and fibrogenesis [6,7]. Previous studies in our lab have shown that soluble egg antigens (SEA) from Schistosoma japonicum could suppress activation and proliferation of HSCs [8]. We found that recombinant SjP40 (rSjP40) can inhibit HSC activation caused by TGF-β1 [10]. Hepatic stellate cells (HSCs) are one of the main cell types involved in liver fibrosis induced by many factors, including schistosomes. Previous studies in our lab have shown that recombinant P40 protein from Schistosoma japonicum (rSjP40) can inhibit HSC activation in vitro. We investigated the role of let-7b in the inhibition of HSC activation by rSjP40
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