title: Expression of apoptosis-associated microRNAs in ethanol-induced acute gastric mucosal injury via JNK pathway.
abstract: MicroRNAs (miRNAs) have been shown to be closely associated with cellular apoptosis, but their involvement in response to ethanol-induced gastric mucosal epithelial cell apoptosis remains largely unknown. The purpose of this study was to investigate the expression profile of apoptosis-associated miRNAs in ethanol-induced acute gastric mucosal injury and the mechanisms underlying injury. Gastric mucosal injury was induced in rats by oral administration of ethanol, and gastric tissues were collected for analysis of gastric ulcer index, apoptosis ratio, caspase-3 activity, and miRNAs expression. Cell cultures of human gastric mucosal epithelial cells (GES-1) were incubated with ethanol to induce apoptosis. Mimics or inhibitors of miRNAs or c-Jun N-terminal kinase (JNK) inhibitor were added to the cell culture medium. GES-1 cells were collected for analysis of apoptosis ratio, caspase-3 activity, miRNAs expression, and protein phosphorylation levels of JNK, p38 mitogen-activated protein kinase (p38MAPK), or extracellular signal-regulated kinase (ERK). In the animal experiments, gastric ulcer index, cellular apoptosis, and caspase-3 activity were significantly increased, accompanied by up-regulation of miR-145 and down-regulation of the microRNAs miR-17, miR-19a, miR-21, miR-181a, and miR-200c. In the human cell culture experiments, the anti-apoptotic effects of miR-19a and miR-21 or pro-apoptotic effect of miR-145 were confirmed by their corresponding mimics or inhibitor; the ethanol-induced GES-1 apoptosis as well as the changes in miRNAs expression were significantly attenuated in the presence of JNK inhibitor. These results demonstrated that miR-145, miR-19a, and miR-21 were the apoptosis-associated miRNAs in gastric mucosal epithelial cells. The regulation of expression of these 3 miRNAs in ethanol-induced GES-1 apoptosis involved the JNK pathway.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, No. 110 Xiang-Ya Road, Changsha 410078, China.
authors.forename: Xiu-Ju
authors.initials: XJ
authors.lastname: Luo
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Dai
authors.forename: Ting-Bo
authors.initials: TB
authors.lastname: Li
authors.forename: Nian-Sheng
authors.initials: NS
authors.lastname: Li
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Zhi-Chun
authors.initials: ZC
authors.lastname: Yang
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C541010:MIRN145 microRNA, human; C549214:MIRN19A microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Apoptosis; Ethanol; Gastric mucosa; JNK pathway; microRNAs