Kruppel-like-factor 10 Expression in progression of diet induced nonalcoholic steatohepatitis in mice

초록

Kruppel-like-factor (KLF) 10 is identified as transforming growth factor (TGF) β inducible early gene and reported to suppress lipogenic genes. Although previous studies reported that TGFβ plays an important role in progression of nonalcoholic steatohepatitis (NASH) by regulating liver fibrosis, the role of KLF10 in NASH has never been explored. Thus we evaluated expression and change of KLF10 in diet induced NASH and in NASH which was alleviated by ursodeoxycholic acid (UDCA). C57BL/6 mice were given high fat and sucrose diet (HFSD) for 48 weeks and the mice were sacrificed at 12, 24 and 48 weeks after the feeding started. 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. After fed with either SD or HFSD for 24 weeks, mice on HFSD were divided into two groups, and fed with HFSD in combination with either 20 mg/kg UDCA or vehicle. 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. Our study showed that KLF10 expression was significantly increased in association with enhance TGFβ gene in diet induced NASH. We also observed that this up-regulation of KLF10 was accompanied by suppressed ChREBP expression These observations suggest a possible role of KLF10 in progression of NASH, and further studies should be warranted to test KLF10 as a target for improving NASH.