title: Up-regulation of Tight-Junction Proteins by p38 Mitogen-Activated Protein Kinase/p53 Inhibition Leads to a Reduction of Injury to the Intestinal Mucosal Barrier in Severe Acute Pancreatitis.
abstract: The aim of this study was to explore the role of the p38 mitogen-activated protein kinase (p38MAPK)/p53 signaling pathway in injury to the intestinal mucosal barrier during severe acute pancreatitis (SAP).
  
  
  
  Both sham operation and SAP groups had 3 subgroups analyzed 3, 6, or 12 hours after the SAP induction. The concentrations of amylase, endotoxin, diamine oxidase, tumor necrosis factor α, and phospho-p38MAPK, p53, and caspase-3 and the messenger RNA levels of zonula occludens protein-1 and occludin in the intestine were measured. Immunohistochemical staining was used to determine the expression of zonula occludens protein-1 and occludin. Pathological changes of the pancreas and intestine were also assessed. Then, rats were randomly assigned to 5 groups-sham operation group, SAP group, 3 groups treated with different concentrations of p38MAPK-inhibitor SB203580-and the abovementioned experiment was repeated and analyzed 6 hours after the SAP induction.
  
  
  
  The phospho-p38MAPK reached a peak value at 6 hours after the SAP induction with obvious pathological injury to the pancreas and intestine. Treatment with SB203580 led to a less damage to the pancreatic and intestinal tissues.
  
  
  
  These results suggest that SAP activates the p38MAPK/p53 signaling pathway and induces injury to the intestinal mucosal barrier, which can be alleviated by inhibiting the p38MAPK/p53 pathway.
authors.affiliation: From the *Department of General Surgery, the Second People's Hospital of Taizhou, Jiangyan District, Taizhou, Jiangsu; †Department of General Surgery, the 97th Hospital of PLA, Xuzhou, Jiangsu; ‡School of Pharmacy, Shanghai Jiao Tong University; and §Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Shanghai; and ∥Science and Technology Department, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ouyang
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Yue-Xian
authors.initials: YX
authors.lastname: Zhou
authors.forename: Wan-Cheng
authors.initials: WC
authors.lastname: Niu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Chang-Bing
authors.initials: CB
authors.lastname: Shen
authors.forename: Ren-Guo
authors.initials: RG
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Li
mesh_terms: D000208:Acute Disease; D000818:Animals; D010195:Pancreatitis; D051381:Rats; D062725:Tight Junction Proteins; D016159:Tumor Suppressor Protein p53; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D062725:Tight Junction Proteins; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases