MicroRNA files in the prevention of intestinal ischemia/reperfusion injury by hydrogen rich saline

Autor: Jian-Pei Liu, Pinjie Huang, Anshun Guo, Weifeng Yao, Lanfen Zeng, Yu Guan, Ziqing Hei, Xiaoyu Lin, Xue Han
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Intestinal Ischemia/Reperfusion Injury
medicine.medical_treatment
Biophysics
Ischemia
Inflammation
Apoptosis
Cell Death & Injury
Pharmacology
medicine.disease_cause
Biochemistry
Cell Line
03 medical and health sciences
0302 clinical medicine
Intestine
Small
medicine
Animals
Intestinal Mucosa
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Research Articles
business.industry
Growth factor
Cell Biology
medicine.disease
Gastrointestinal
Renal & Hepatic Systems
Mice
Inbred C57BL
Disease Models
Animal
Intestinal Diseases
MicroRNAs
030104 developmental biology
Gene Expression Regulation
Oxidative stress
030220 oncology & carcinogenesis
Reperfusion Injury
Saline Solution
medicine.symptom
business
Transcriptome
Reperfusion injury
Injections
Intraperitoneal
Signal Transduction
Zdroj: Bioscience Reports
ISSN: 1573-4935
Popis: Background: Hydrogen-rich saline (HRS) has been proven effective against ischemia/reperfusion (I/R) injury. However, knowledge on the underlying signaling events remain poor. Having recent highlight of microRNAs (miRNAs) in mediating intestinal I/R injury, we hypothesized that HRS may protect intestine against I/R injury by regulating miRNAs. Method: Mice were given intraperitoneal injection of saline or HRS once daily for five consecutive days before undergoing intestinal I/R that was induced by 60-min ischemia followed by 180-min reperfusion of superior mesenteric artery. The intestine was collected for histopathological assay, miRNA microarray profiling, Real-Time PCR, and Western blotting. Next, miR-199a-3p mimics or inhibitors were transfected into IEC-6 cells to explore the relationship between HRS treatment and miR-199a-3p. Results: I/R-induced mucosal injury and epithelial cells apoptosis were attenuated by HRS pretreatment. A total of 64 intestinal I/R-responsive miRNAs were altered significantly by HRS pretreatment, in which we validated four novel miRNAs with top significance by Real-Time PCR, namely miR-199a-3p, miR-296-5p, miR-5126, and miR-6538. Particularly, miR-199a-3p was drastically increased by I/R but reduced by HRS. Computational analysis predicts insulin-like growth factor (IGF)-1, mammalian target of rapamycin (mTOR), and phosphoinositide-3-kinase (PI3K) regulatory subunit 1 as targets of miR-199a-3p, suggesting involvement of the pro-survival pathway, IGF- 1/PI3K/Akt/mTOR. In in vitro experiment, HRS treatment reduced miR-199a-3p level, increase IGF-1, PI3K and mTOR mRNA expression, restore IEC-6 cells viability, and this protective effects were reversed under miR-199a-3p mimics treatment. Conclusion: Collectively, miR-199a-3p may serve a key role in the anti-apoptotic mechanism of HRS that contributes to its protection of the intestine against I/R injury.
Databáze: OpenAIRE
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