Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression  

作　　者：Shuang Liu Man Liu Meng-lin Zhang Cui-zhe Wang Yin-liang Zhang Yu-jie Zhang Chun-yuan Du Su-fang Sheng Wei Wang Ya-tong Fan Jia-ni Song Jin-can Huang Yue-yao Feng Wei Qiao Jin-long Huang Yu-hui Li Lu Zhou Jun Zhang Yong-sheng Chang 

机构地区：[1]Key Laboratory of Immune Microenvironment and Disease(Ministry of Education),Tianjin Key Laboratory of Cellular Homeostasis and Disease,Department of Physiology and Pathophysiology,Tianjin Medical University,Tianjin 300052,China [2]Department of Basic Medicine,Shihezi University School of Medicine,Shihezi 832000,China [3]Key Laboratory of Biotechnology of Hubei Province,Key Laboratory of Biotechnology of Chinese Traditional Medicine,National&Local Joint Engineering Research Center of High-throughput Drug Screening Technology,Hubei University,Wuhan 430062,China [4]Department of Gastroenterology and Hepatology,Tianjin Medical University General Hospital,Tianjin 300052,China

出　　处：《Acta Pharmacologica Sinica》2022年第9期2362-2372,共11页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(grants 81730024 and 81825004);the National Key Research and Development Program of China(2018YFA0800601);the Scientific and Technological Research Project of Xinjiang Production and Construction Corps(grants 2018AB018 and 2021AB028);the Tianjin Research Innovation Project for Postgraduate Students(2021YJSB259).

摘　　要：Bile acid(BA)homeostasis is regulated by the extensive cross-talk between liver and intestine.Many bile-acid-activated signaling pathways have become attractive therapeutic targets for the treatment of metabolic disorders.In this study we investigated the regulatory mechanisms of BA in the intestine.We showed that the BA levels in the gallbladder and faeces were significantly increased,whereas serum BA levels decreased in systemic Krüppel-like factor 9(Klf9)deficiency(Klf9^(-/-))mice.These phenotypes were also observed in the intestine-specific Klf9-deleted(Klf9vil^(-/-))mice.In contrast,BA levels in the gallbladder and faeces were reduced,whereas BA levels in the serum were increased in intestinal Klf9 transgenic(Klf9Rosa26+/+)mice.By using a combination of biochemical,molecular and functional assays,we revealed that Klf9 promoted the expression of apical sodium-dependent bile acid transporter(Asbt)in the terminal ileum to enhance BA absorption in the intestine.Reabsorbed BA affected liver BA synthetic enzymes by regulating Fgf15 expression.This study has identified a previously neglected transcriptional pathway that regulates BA homeostasis.

关 键 词：Klf9 ASBT bile acid Fgf15 

分 类 号：R285.5[医药卫生—中药学]