title: miRNA-338-3p/CDK4 signaling pathway suppressed hepatic stellate cell activation and proliferation.
abstract: BACKGROUND
  Activated hepatic stellate cell (HSC) is the main fibrogenic cell type in the injured liver. miRNA plays an important role in activation and proliferation of HSC.
  
  
  METHODS
  Our previous study examined the expression profiles of microRNAs in quiescent and activated HSC. Real-time PCR and western blot were used to detect the expression of Collagen type I (Col 1) and Alpha-Smooth Muscle Actin (α-SMA). CCK-8 and Edu assay was used to measure the proliferation rate of HSC. Luciferase reporter gene assay was used to tested the binding between miR-338-3p and Cyclin-dependent kinase 4 (CDK4).
  
  
  RESULTS
  We found overexpression of miR-338-3p could inhibit Col 1 and α-SMA, two major HSC activation markers, whereas miR-338-3p inhibitor could promote them. Besides, miR-338-3p overexpression could suppress the growth rate of HSC. Further, we found that CDK4, a pleiotropic signaling protein, was a direct target gene of miR-338-3p. Moreover, we found that overexpression of CDK4 could block the effects of miR-338-3p.
  
  
  CONCLUSIONS
  We found miR-338-3p is an anti-fibrotic miRNA which inhibits cell activation and proliferation. Our findings suggest that miR-338-3p/CDK4 signaling pathway participates in the regulation of HSC activation and growth and may act as a novel target for further anti-fibrotic therapy.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Bensong
authors.initials: B
authors.lastname: Duan
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. doctorhjf@foxmail.com.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Respiration, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Tongyangzi
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Digestive Endoscopic Center, Department of Gastroenterology, South Building General Hospital of PLA, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China. 15900611429@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: National Engineering Center for Biochip at Shanghai, Shanghai, China. hengjun_gao@tongji.edu.cn.|Department of Gastroenterology, Institute of Digestive Diseases, Tongji University School of Medicine, Shanghai, China. hengjun_gao@tongji.edu.cn.
authors.forename: Hengjun
authors.initials: H
authors.lastname: Gao
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000503:physiopathology; D035683:MicroRNAs / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000199:Actins; D024042:Collagen Type I; D051358:Cyclin-Dependent Kinase 4; D035683:MicroRNAs; C573089:MIRN338 microRNA, rat; C498862:Acta2 protein, rat; C495903:Cdk4 protein, rat
keywords: CDK4; Liver fibrosis; miR-338