Jianling Zhang1, Huanjun Huang2. 1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, P. R. China. 2. Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 430030, Hubei, P. R. China.
Abstract
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease, which may develop into end-stage liver disease and endanger human life. miR-122-5p may be related to the progression of NAFLD disease, but the specific regulation mechanism is still unknown. It is helpful for us to optimize the prevention or treatment strategy of NAFLD. METHODS: Real-time PCR was applied to test miR-122-5p and KIF5B in serum, rat liver tissue induced by high fat diet (HFD), and primary hepatocytes exposed to oleic acid ester and palmitate (FFA) of NAFLD patients. The role of miR-122-5p on inflammatory factors (MCP-1, TNF-α, IL-10) and liver injury markers (AST, ALT) in vivo and in vitro was analyzed. RESULTS: miR-122-5p and KIF5B were both highly expressed in NAFLD patients' serum, rat liver tissue and primary hepatocytes, while KIF5B was low expressed. miR-122-5p expression enhanced with the increase of HFD feeding time. The dual luciferase reporter gene assay system confirmed that there was a targeting relationship between miR-122-5p and KIF5B, indicating that KIF5B and protein level were evidently up-regulated in primary hepatocytes. Down-regulation of miR-122-5p was helpful to improve the liver weight/body weight ratio (liver index) level of rats, as well as the levels of triglyceride (TG), inflammatory factors and liver injury markers in liver tissues in vivo and in vitro. Phosphorylation of AMPK/AKT pathway-related proteins and fat metabolism-related factors in rat liver tissues and cells in primary hepatocytes were notably reduced, while down-regulation of miR-122-5p was helpful to restore activation of the pathway and increase the level of fat metabolism-related factors. CONCLUSION: Decrease of miR-122-5p can target and enhance KIF5B, which can be applied for treating NAFLD. AJTR
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease, which may develop into end-stage liver disease and endanger human life. miR-122-5p may be related to the progression of NAFLD disease, but the specific regulation mechanism is still unknown. It is helpful for us to optimize the prevention or treatment strategy of NAFLD. METHODS: Real-time PCR was applied to test miR-122-5p and KIF5B in serum, rat liver tissue induced by high fat diet (HFD), and primary hepatocytes exposed to oleic acid ester and palmitate (FFA) of NAFLD patients. The role of miR-122-5p on inflammatory factors (MCP-1, TNF-α, IL-10) and liver injury markers (AST, ALT) in vivo and in vitro was analyzed. RESULTS:miR-122-5p and KIF5B were both highly expressed in NAFLD patients' serum, rat liver tissue and primary hepatocytes, while KIF5B was low expressed. miR-122-5p expression enhanced with the increase of HFD feeding time. The dual luciferase reporter gene assay system confirmed that there was a targeting relationship between miR-122-5p and KIF5B, indicating that KIF5B and protein level were evidently up-regulated in primary hepatocytes. Down-regulation of miR-122-5p was helpful to improve the liver weight/body weight ratio (liver index) level of rats, as well as the levels of triglyceride (TG), inflammatory factors and liver injury markers in liver tissues in vivo and in vitro. Phosphorylation of AMPK/AKT pathway-related proteins and fat metabolism-related factors in rat liver tissues and cells in primary hepatocytes were notably reduced, while down-regulation of miR-122-5p was helpful to restore activation of the pathway and increase the level of fat metabolism-related factors. CONCLUSION: Decrease of miR-122-5p can target and enhance KIF5B, which can be applied for treating NAFLD. AJTR
Authors: Noura S Abul-Husn; Xiping Cheng; Alexander H Li; Yurong Xin; Claudia Schurmann; Panayiotis Stevis; Yashu Liu; Julia Kozlitina; Stefan Stender; G Craig Wood; Ann N Stepanchick; Matthew D Still; Shane McCarthy; Colm O'Dushlaine; Jonathan S Packer; Suganthi Balasubramanian; Nehal Gosalia; David Esopi; Sun Y Kim; Semanti Mukherjee; Alexander E Lopez; Erin D Fuller; John Penn; Xin Chu; Jonathan Z Luo; Uyenlinh L Mirshahi; David J Carey; Christopher D Still; Michael D Feldman; Aeron Small; Scott M Damrauer; Daniel J Rader; Brian Zambrowicz; William Olson; Andrew J Murphy; Ingrid B Borecki; Alan R Shuldiner; Jeffrey G Reid; John D Overton; George D Yancopoulos; Helen H Hobbs; Jonathan C Cohen; Omri Gottesman; Tanya M Teslovich; Aris Baras; Tooraj Mirshahi; Jesper Gromada; Frederick E Dewey Journal: N Engl J Med Date: 2018-03-22 Impact factor: 91.245