TRPM7 is involved in IL-6-induced hepatocyte proliferation via the STAT3 pathway

Acta Universitatis Medicinalis Anhui 2020 01 v.55 109-114     font:big middle small

Found programs:

Authors:Cui Zhihua; Fang Ling; Li Lingling

Keywords:TRPM7;hepatocyte proliferation;STAT3

DOI:10.19405/j.cnki.issn1000-1492.2020.01.023

〔Abstract〕 Objective To investigate the expression changes of transient receptor potential melastatin 7(TRPM7) during liver regeneration after partial hepatectomy(PHx) in mice and the effect on proliferation of hepatocytes(L-02). Methods Using 70% PHx liver regeneration model in mice, hematoxylin-eosin(HE) staining was used to observe liver pathology,ELASA was used to detect alanine aminotransferase( ALT) and aspartate aminotransferase( AST) protein levels at different times( 0 h,12 h,24 h,36 h,48 h,72 h,5 d,7 d) after surgery. Western blot analysis was used to detect the expression of TRPM7 and PCNA in liver tissues at different times after operation. L-02 cells proliferation was induced by recombinant human interleukin 6( IL-6),and the expression of TRPM7 was detected by Western blot method. TRPM7 channel was blocked by 2-Aminoethoxydiphenyl borate( 2-APB),L-02 cells viability was detected by MTT assay,and protein expressions of proliferating cell nuclear antigen( PCNA),phosphorylated signal transducers and activators of transcription 3( p-STAT3) were detected by Western blot method. Results After PHx,it was observed that tissue hyperplasia was obvious,the cell volume became larger,the proliferating hepatocyte cord was arranged with different degrees of disorder while inflammatory cell infiltration was accompanied. ALT and AST protein levels increased significantly after PHx and peaked at 12 h,and then gradually decreased to normal levels. The protein level of TRPM7 in mouse liver tissue increased significantly after PHx and lasted for 72 h( P<0. 05),which was correlated with changes in cell proliferation protein PCNA expression levels.IL-6 induced a significant increase in L-02 cell viability and TRPM7 protein levels. IL-6-induced increase of hepatocyte viability was inhibited by 2-APB in a concentration-dependent manner,and PCNA and P-STAT3 levels were also decreased after blocking TRPM7 channel. Conclusion TRPM7 increased expression during liver regeneration and hepatocyte proliferation,and inhibition of TRPM7 channel by 2-APB inhibited hepatocyte proliferation through reducing STAT3 phosphorylation,indicating that TRPM7 plays an important role in hepatocyte proliferation.