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Background  Kruppel-like-factor (KLF) 10 is identified as transforming growth factor (TGF) β inducible early gene and is reported to suppress lipogenic genes. Although previous studies report that TGFβ plays an important role in progression of nonalcoholic steatohepatitis (NASH) by regulating liver fibrosis, the association of KLF10 and NASH has never been explored. Thus we evaluated expressions and changes of  KLF10  in diet induced NASH and in NASH which was alleviated by ursodeoxycholic acid (UDCA). We also assessed  KLF10  in quiescent and activated hepatic stellate cells (HSCs).    Methods  C57BL/6 mice were given high fat, sucrose diet (HFSD) at least for 12 weeks up to 48 weeks and sacrificed at 12, 24 and 48 weeks thereafter. In other groups, either standard diet (SD) or HFSD was given for 24 weeks at which point mice fed with HFSD were divided into two groups, and were given either UDCA in combination with HFSD or vehicle with HFSD. Mice under SD were given vehicle. HSCs were isolated from C57BL/6 mice in order to evaluated KLF10 expression in activated HSCs.    Results  The mice were found to acquire liver steatosis and inflammation starting from week 12 of HFSD feeding, although significant liver fibrosis was noticed by week 24. Increased  TGFβ  and  collagen α1(I)  ( Col1α(I) ) expression was also apparent from week 24. However, expression of  KLF10  mRNA started to increase from week 12, earlier than  TGFβ  gene. Up-regulation of  KLF10  was accompanied by suppressed carbohydrate response element-binding protein (ChREBP) that is known to be protective against insulin resistance. The mice fed with HFSD and UDCA had decreased  Colα(I)  mRNA that was coincided with reduced  TGFβ  and  KLF10  expression. Expression of  ChREBP  was also recovered by UDCA administration. Enhanced  KLF10  was noticed in activated HSCs when quiescent cell showed minimal expression.    Conclusions  Our study demonstrated that  KLF10  expression was significantly increased in diet induced NASH and collagen producing activated HSCs. We also noticed that this up-regulation of  KLF10  was accompanied by increased TGFβ signaling genes and suppressed  ChREBP  expression. These observations suggest possible association of KLF10 and NASH progression.

Progression of diet induced nonalcoholic steatohepatitis is accompanied by increased expression of kruppel-like-factor 10 in mice