title: miRNA regulation of liver growth after 50% partial hepatectomy and small size grafts in rats.
abstract: BACKGROUND
  The molecular mechanisms underlying the growth of small size grafts and the remaining livers are poorly understood. MicroRNAs (miRNAs) negatively modulate expression of genes that are involved in cellular function and metabolism. The aim of this study is to identify critical miRNA species that modulate the growth of small grafts and the remaining livers after partial hepatectomy (PH).
  
  
  METHODS
  Small size graft liver transplantation was performed in rats. Liver tissue was harvested after transplant or PH for the determination of miRNA expression profile, and the data were confirmed by quantitative reverse-transcriptase polymerase chain reaction. The genes involved in cell cycle and proliferation were analyzed by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemical staining.
  
  
  RESULTS
  Compared with control liver, miR_122a, Let_7b, and miR_26a were reduced by more than 90% in 45% volume grafts. In the remaining livers after 50% PH, 30 miRNAs were down-regulated by more than 50%, and among them, miR_22a, miR_26a, miR_30b, Let_7f, and Let_7g were markedly decreased. A negative correlation existed between down-regulated miRNAs and highly up-regulated genes involved in cell cycle and proliferation in the remaining livers. Moreover, overexpression of miR_26a markedly down-regulated cyclin E2 protein levels and significantly decreased proliferation of HepG2 cells.
  
  
  CONCLUSIONS
  Down-regulated miRNAs play a pivotal role in promoting the growth of small size grafts and the remaining livers. The negative correlation between down-regulated miRNAs and up-regulated genes suggests that these specific miRNAs participate in the modulation of a growth response in both living donors and small size graft recipients.
authors.affiliation: Department of Internal Medicine, Transplant Research Program, University of California, Davis Medical Center, Sacramento, CA 95817, USA. jdwu@ucdavis.edu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Musab
authors.initials: M
authors.lastname: Murad
authors.forename: Yi-Yao
authors.initials: YY
authors.lastname: Cui
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yao
authors.forename: Senthil K
authors.initials: SK
authors.lastname: Venugopal
authors.forename: Kevin
authors.initials: K
authors.lastname: Dawson
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D019927:Cyclin E / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D006498:Hepatectomy; D008099:Liver / Q000254:growth & development* / Q000601:surgery*; D008115:Liver Regeneration / Q000502:physiology*; D016031:Liver Transplantation / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology
chemical_list: C503690:Ccne2 protein, rat; D019927:Cyclin E; C556274:MIRN26 microRNA, rat; D035683:MicroRNAs