title: Transforming growth factor (TGF)-β-induced microRNA-216a promotes acute pancreatitis via Akt and TGF-β pathway in mice.
abstract: BACKGROUND
  Both transforming growth factor β (TGF-β) and MicroRNA-216a (miR-216a) were reported to be upregulated during acute pancreatitis (AP). Moreover, miR-216a can be induced by TGF-β.
  
  
  OBJECTIVE
  This study aimed to investigate how TGF-β and miR-216a involved in the pathogenesis of AP both in a mouse model and in rat pancreatic acinar AR42J cells.
  
  
  METHODS
  Cerulein-induced AP mouse model was established and pretreated with a TGF-β inhibitor, SB431542. Serum amylase, lipase, tumor necrosis factor (TNF)-α, interleukin 6 (IL-6), TGF-β and histopathological changes of pancreas were determined. Expression of miR-216a was detected by quantitative real-time RT-PCR. Bioinformatics was utilized to predict the targets of miR-216a. Expression levels of phosphatase and tensin homolog (PTEN), mothers against decapentaplegic homolog 7 (Smad7), TGF-β receptor I, total Akt and pAkt were detected by Western blot.
  
  
  RESULTS
  SB431542 significantly decreased serum amylase, lipase, TNF-α, IL-6, TGF-β, histopathological changes of pancreas and expression of miR-216a in cerulein-induced mouse (P < 0.05). TGF-β induced miR-216a in AR42J cells. PTEN and Smad7 were identified to be the possible targets of miR-216a. Transfection of miR-216a mimics (or inhibitors) in AR42J cells downregulated (or upregulated) the expression of PTEN and Smad7, thus affected the expression of downstream pAkt and TGF-β receptor I. The expression changes of these protein caused by miR-216a can be regulated by SB431542 both in mouse model and AR42J cells.
  
  
  CONCLUSIONS
  TGF-β promotes AP by inducing miR-216a targeting PTEN and Smad7, thus through PI3K/Akt and TGF-β feedback pathway.
authors.affiliation: Department of General Surgery, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong Province, People's Republic of China, Jianzhang0203@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Ning
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Meisheng
authors.initials: M
authors.lastname: Bi
authors.forename: Dianliang
authors.initials: D
authors.lastname: Zhang
authors.forename: Jianli
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000208:Acute Disease; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C553402:MIRN216 microRNA, mouse; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D051906:Smad7 Protein; C497807:Smad7 protein, mouse; D016212:Transforming Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse