TET3 mediates the activation of human hepatic stellate cells via modulating the expression of long non-coding RNA HIF1A-AS1.

Abstract

Activated Hepatic stellate cells (HSCs) play a critical role in liver fibrosis and a lot of efforts have been made to dissect the underlying mechanism involved in activation of HSCs. However, the underlying mechanism remains douteux up to now. In the present study, we found that TET3, one member of ten-eleven translocation (TET) protein family, reduced significantly in HSCs LX-2 activated by TGF-β1. To study the function of TET3 in activation of HSCs, knockdown was performed by RNA interference. Results showed that cell proliferation rise significantly and cell apoptosis reduce obviously after knockdown of TET3. Meanwhile, IHC showed that the expression of α-SMA rise significantly compared to control. These results indicated that TET3 is closely associated with the activation of HSCs. Further studies found that long non-coding RNA HIF1A-AS1 was reduced significantly in LX-2 cell after treatment with siRNA for TET3. The result hinted that TET3 activate HSCs through modulating the expression of HIF1A-AS1. To confirm this hypothesis, RNA interference was performed to silence the HIF1A-AS1. Results showed that HIF1A-AS1 silencing lead to enhancing in cell proliferation and declining apoptosis. Taken together, TET3 can mediate the activation of HSCs via modulating the expression of the long non-coding RNA HIF1A-AS1.