Hepatic FXR-FGF4 is required for bile acid homeostasis via an FGFR4-LRH-1 signal node under cholestatic stress
文献类型：期刊论文
| 作者 | Song, Lintao5,6; Hou, Yushu5; Xu, Da5; Dai, Xijia5; Luo, Jianya5; Liu, Yi5; Huang, Zhuobing5; Yang, Miaomiao5; Chen, Jie5; Hu, Yue5 |
| 刊名 | CELL METABOLISM
 |
| 出版日期 | 2025-01-07 |
| 卷号 | 37期号:1页码:104-+ |
| ISSN号 | 1550-4131 |
| DOI | 10.1016/j.cmet.2024.09.008 |
| 英文摘要 | Bile acid (BA) homeostasis is vital for various physiological processes, whereas its disruption underlies cholestasis. The farnesoid X receptor (FXR) is a master regulator of BA homeostasis via the ileal fibroblast growth factor (FGF)15/19 endocrine pathway, responding to postprandial or abnormal transintestinal BA flux. However, the de novo paracrine signal mediator of hepatic FXR, which governs the extent of BA synthesis within the liver in non-postprandial or intrahepatic cholestatic conditions, remains unknown. We identified hepatic Fgf4 as a direct FXR target that paracrinally signals to downregulate Cyp7a1 and Cyp8b1. The effect of FXR-FGF4 is mediated by an uncharted intracellular FGF receptor 4 (FGFR4)-LRH-1 signaling node. This liver-centric pathway acts as a first-line checkpoint for intrahepatic and transhepatic BA flux upstream of the peripheral FXR-FGF15/19 pathway, which together constitutes an integral hepatoenteric control mechanism that fine-tunes BA homeostasis, counteracting cholestasis and hepatobiliary damage. Our findings shed light on potential therapeutic strategies for cholestatic diseases. |
| WOS关键词 | NEGATIVE FEEDBACK-REGULATION ; FARNESOID-X-RECEPTOR ; MOLECULAR-BASIS ; LIVER ; PATHOPHYSIOLOGY ; GENETICS ; CASCADE ; ROLES ; SERUM ; FGF15 |
| 资助项目 | National Natural Science Foundation of China[92357304] ; National Natural Science Foundation of China[82373934] ; National Natural Science Foundation of China[82002965] ; National Natural Science Foundation of China[U22A20385] ; Natural Science Foundation of Zhejiang Province[LZ23H310002] ; Natural Science Foundation of Zhejiang Province[LDQ24H310001] ; Science Technology Department of Wenzhou[ZY2021022] ; Postdoctoral Fellowship Program of CPSF[GZB20230532] ; Scientific Research Center of Wenzhou Medical University ; Oujiang Laboratory[OJQDSP202205] |
| WOS研究方向 | Cell Biology ; Endocrinology & Metabolism |
| 语种 | 英语 |
| WOS记录号 | WOS:001413381700001 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316311]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Song, Lintao; Li, Xiaokun; Huang, Zhifeng |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Renji Hosp, Div Gastroenterol & Hepatol,Sch Med, Shanghai 200001, Peoples R China 3.Wenzhou Med Univ, Dept Infect Dis, Affiliated Hosp 1, Wenzhou 325035, Zhejiang, Peoples R China 4.Wenzhou Med Univ, Dept Hepatol, NAFLD Res Ctr, Affiliated Hosp 1, Wenzhou 325035, Zhejiang, Peoples R China 5.Wenzhou Med Univ, Sch Pharmaceut Sci, Oujiang Lab Zhejiang Lab Regenerat Med Vis & Brai, Natl Key Lab Macromol Drugs & Large Scale Prepart, Wenzhou 325035, Zhejiang, Peoples R China 6.Wenzhou Med Univ, Translat Med Lab, Affiliated Hosp 1, Wenzhou 325035, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Song, Lintao,Hou, Yushu,Xu, Da,et al. Hepatic FXR-FGF4 is required for bile acid homeostasis via an FGFR4-LRH-1 signal node under cholestatic stress[J]. CELL METABOLISM,2025,37(1):104-+. |
| APA | Song, Lintao.,Hou, Yushu.,Xu, Da.,Dai, Xijia.,Luo, Jianya.,...&Huang, Zhifeng.(2025).Hepatic FXR-FGF4 is required for bile acid homeostasis via an FGFR4-LRH-1 signal node under cholestatic stress.CELL METABOLISM,37(1),104-+. |
| MLA | Song, Lintao,et al."Hepatic FXR-FGF4 is required for bile acid homeostasis via an FGFR4-LRH-1 signal node under cholestatic stress".CELL METABOLISM 37.1(2025):104-+. |
入库方式： OAI收割
来源：上海药物研究所
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