Hong-Yi Zhang1, Fang Wang2, Xuyong Chen1, Xinrao Meng1, Chenzhao Feng3, Jie-Xiong Feng4. 1. Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China. 2. Department of Neurology, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, 430014, China. 3. Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 4. Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China. jackpsjx@tom.com.
Abstract
PURPOSE: The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR. METHODS: Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated. RESULTS: Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation. CONCLUSIONS: Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2.
PURPOSE: The roles of commensal bacteria after intestinal ischemia and reperfusion (IIR) are unclear. In current study, we aim to investigate the effects and underlying mechanisms of commensal bacteria in injury and epithelial restitution after IIR. METHODS: Commensal gut bacteria were deleted by broad-spectrum antibiotics in mice. IIR was induced by clamping superior mesenteric artery. Intestinal injury, permeability, epithelial proliferation, and proinflammatory activity of mesenteric lymph were investigated. RESULTS: Commensals deletion improved mice survival in the early phase, but failed to improve the overall survival at 96 h after IIR. Commensals deletion reduced proliferation of intestinal epithelial cells (IEC) and augmented proinflammatory activity of mesenteric lymph after IIR. Lipopolysaccharides (LPS) supplement promoted IEC proliferation and improved survival in mice with commensals deletion after IIR. LPS induced production of prostaglandin E2 (PGE2) in mucosa via toll-like receptor 4-NFκB-cyclooxygenase 2 pathway. PGE2 enhanced IEC proliferation in vivo, which was preceded by activation of Akt and extracellular signal-regulated kinase (ERK) 1/2. Blocking of EGFR, PI3K/Akt activity abolished LPS-induced IEC proliferation. CONCLUSIONS: Commensal bacteria are essential for epithelial restitution after IIR, which enhance IEC proliferation via induction of PGE2.
Entities:
Keywords:
Commensal bacteria; Epithelium; Intestinal ischemia and reperfusion; Proliferation
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