title: Improved autophagic flux is correlated with mTOR activation in the later recovery stage of experimental acute pancreatitis.
abstract: OBJECTIVE
  Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms.
  
  
  METHODS
  AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity.
  
  
  RESULTS
  AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury.
  
  
  CONCLUSIONS
  Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Wen-Huan
authors.initials: WH
authors.lastname: Dou
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Chuang-Ying
authors.initials: CY
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Duan-Min
authors.initials: DM
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Jian-Zong
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Qian
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China.
authors.forename: Gui-Lian
authors.initials: GL
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Soochow 215004, China. Electronic address: sfwang59@sina.cn.
authors.forename: Shao-Feng
authors.initials: SF
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D018450:Disease Progression; D020287:In Situ Nick-End Labeling; D008247:Lysosomes / Q000502:physiology; D008297:Male; D010195:Pancreatitis / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases
keywords: Acute pancreatitis; Apoptosis; Autophagic flux; Lamp-2; Necrosis; mTOR