Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8258793 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2018 | 50 Pages |
Abstract
Studies have indicated that the definitive engraftment and transdifferentiation potential of stem cells do not seem crucial for its property of tissue repair. Our previous study showed that transplantation of adipose-derived mesenchymal stem cells (ADMSCs) enhanced the healing of sutured gastric perforation. This study aimed to investigate the paracrine role of ADMSCs in the experimental gastric mucosal injury. Normoxia-conditioned medium (Nor CM) and hypoxia (HPO) CM were obtained after culturing ADMSCs in 20% O2 and 5% O2 for 48Â h. Cell migration, proliferation, viability, and angiogenesis in vitro were significantly enhanced upon incubation with CM, especially the HPO CM. Experiments in vivo using a rodent model of gastric ulcer demonstrated that HPO CM treatment significantly accelerated wound healing by suppressing inflammation and promoting neovascularization and re-epithelization. Meanwhile, the infusion of HPO CM activated the COX2-PGE2 axis both in vitro and in vivo. And the upregulation of COX2 was further dependent on the activation of ErK1/2-MAPK pathway. In addition, vascular endothelial growth factor, tissue inhibitors of metalloproteinases-1, and chemokine (C-C motif) ligand 20 (CCL-20) were analyzed as being highly abundant factors secreted by ADMSCs under hypoxic condition. Notably, the blockade of CCL-20 abrogated the HPO CM-induced COX2 signaling in the primary gastric mucosal epithelial cells, while incubation with recombinant CCL-20 increased the expression of COX2. In conclusion, the secretome from hypoxia-conditioned ADMSCs facilitates the repair of gastric mucosal injury through the enhancement of angiogenesis and re-epithelization, as well as the activation of COX2-PGE2 axis with a paracrine activity involving CCL-20 factor.
Keywords
α-SMABMETIMP-1PFAhpfcox2DAPIEVSPGE2mPGES-1GAPDHADMSCsCCK-8DMEMFBSchemokine (C-C motif) ligand 20GECsHMVECsDulbecco's modified Eagle MediumERK1/2H&EMAPKGastric mucosal injurySprague-DawleyOmeprazoleTUNELExtracellular vesiclesGastrointestinalfetal bovine serumAdipose-derived mesenchymal stem cellscyclooxygenase 2Conditioned mediumbasement membrane extractVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelingsecretomehaematoxylin and eosinHypoxiaparaformaldehydemitogen-activated protein kinasemicrosomal prostaglandin E synthase-1Prostaglandin E2extracellular signal-regulated kinase 1/2glyceraldehyde 3-phosphate dehydrogenase
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Authors
Xianfeng Xia, Philip Wai Yan Chiu, Ping Kuen Lam, Wai Ching Chin, Enders Kwok Wai Ng, James Yun Wong Lau,