KGF inhibits hypoxia-induced intestinal epithelial cell apoptosis by upregulating AKT/ERK pathway-dependent E-cadherin expression
- PMID: 30021369
- DOI: 10.1016/j.biopha.2018.06.091
KGF inhibits hypoxia-induced intestinal epithelial cell apoptosis by upregulating AKT/ERK pathway-dependent E-cadherin expression
Abstract
Objective: Intestinal ischemia-reperfusion (I/R) causes direct cellular damage, and the potential injury to the mucosal structure and barrier function. Keratinocyte growth factor (KGF) is highly expressed in gastrointestinal tract and exerts beneficial effects for intestinal epithelial growth and maintenance. E-cadherin plays an important role in intestinal epithelium renewal. However, the regulatory role of KGF on E-cadherin levels and I/R-induced apoptosis remain to be explored. The present study aimed to identify the effect of KGF on E-cadherin expression and I/R-induced intestinal epithelial cell apoptosis.
Methods: Caco2 cells were treated with KGF (100 ng/ml) for 0, 4, 8, 12, and 24 h under hypoxia or normoxia. An E-cadherin-knockdown model was successfully established by treatment with E-cadherin RNAi. Western blotting and immunofluorescence labeling were performed to assess E-cadherin expression. Levels of PI3K|[sol]|Akt/mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinase (PI3K|[sol]|Akt)/PI3K|[sol]|Akt pathway-related proteins, and apoptosis-related proteins were also detected by western blot. Finally, a rat model of acute intestinal I/R was established and treated with KGF. Hematoxylin-eosin (HE), terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and immunofluorescence staining were performed to detect morphological changes in intestinal mucosal epithelium and Caco2 cell apoptosis.
Results: KGF enhanced E-cadherin expression in differentiated intestinal epithelial cells under hypoxia via AKT/extracellular-regulated kinase (ERK) pathway regulation. In vitro, E-cadherin downregulation aggravates hypoxia-induced intestinal epithelial cell apoptosis. In the rat model, KGF increased E-cadherin expression, which was associated with the reduced apoptosis.
Conclusions: KGF exerts protective effects on intestinal epithelial cells under hypoxia by elevating E-cadherin levels or activating AKT/ERK signaling.
Keywords: AKT/ERK pathway; Apoptosis; E-cadherin; Hypoxia; Intestinal ischemia-reperfusion; KGF.
Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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