title: Suppression of MicroRNA-219-5p Activates Keratinocyte Growth Factor to Mitigate Severity of Experimental Cirrhosis.
abstract: OBJECTIVE
  Keratinocyte growth factor (KGF) plays a critical role in prevention of cirrhosis and enhancement of liver regeneration. However, the molecular regulation of KGF in liver is unknown. MicroRNAs (miRNAs) control the pathogenesis of cirrhosis, whereas the exact involved miRNAs and molecular signaling pathways remain ill-defined. Here we addressed these questions.
  
  
  METHODS
  We examined the correlation of the levels of miR-219-5p and KGF in the liver biopsies from patients with liver diseases. The effects of overexpression or suppression of miR-219-5p on KGF were examined in both human and mouse hepatic stellate cells (HSCs). Bioinformatics analysis was applied to examine the binding of human/mouse miR-219-5p to the 3'-UTR of human/mouse KGF mRNA, respectively. Finally, adeno-associated viruses carrying antisense of miR-219-5p were infused into the liver from the mice that had developed cirrhosis by carbon tetrachloride (CCl4), and the effects on KGF levels and liver damage and function were examined.
  
  
  RESULTS
  The levels of miR-219-5p and KGF in the liver biopsies were inversely correlated. MiR-219-5p inhibited KGF expression in both human and mouse HSCs, through directly binding the 3'-UTR of KGF mRNA. Expression of antisense of miR-219-5p significantly attenuated the levels of liver fibrosis, portal hypertension and sodium retention caused by CCl4.
  
  
  CONCLUSIONS
  Suppression of miR-219-5p may benefit the liver regeneration and prevent cirrhosis through increasing KGF.
authors.affiliation: Emergency Department, Chinese PLA General Hospital, Beijing, (China).
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Xiang
authors.initials: X
authors.lastname: Cui
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Cong
authors.initials: C
authors.lastname: Feng
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Faqin
authors.initials: F
authors.lastname: Lv
authors.forename: Tanshi
authors.initials: T
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002251:Carbon Tetrachloride; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000235:genetics* / Q000473:pathology*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C578248:MIRN219 microRNA, human; C000609357:MIRN219 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D002251:Carbon Tetrachloride