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Published on: September 9, 2022
MicroRNA-146a overexpression alleviates intestinal ischemia/reperfusion-induced acute lung injury in mice
1Department of Anesthesiology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, Guangdong 518028, P.R. China.
Abstract:
Previous studies have shown that microRNAs (miRs), such as miR-146a play an important role in the pathogenesis of intestinal ischemia/reperfusion (I/R)-induced injury; however, the role of miR-146a in intestinal I/R-induced acute lung injury has not been elucidated. An intestinal I/R-induced injury mouse model was established in the present study by clamping the superior mesenteric artery and expression levels of miR-146a in intestinal and lung tissue samples were evaluated using reverse transcription-quantitative PCR (RT-qPCR). Intestinal and lung histopathological characteristics in mice with intestinal I/R-induced injury were assessed by hematoxylin and eosin staining, and mRNA and protein expression levels in intestinal and lung tissue samples were evaluated using RT-qPCR and western blotting, respectively. miR-146a expression was significantly downregulated in the intestinal and lung tissue samples of mice with intestinal I/R-induced injury. Intestinal I/R injury-induced histopathological changes in the lung and intestines, and pulmonary edema in mice transduced with an adenoviral miR-146a-overexpression vector (the miR-146a overexpression group) were alleviated. mRNA expression levels of TNF-α, IL-1β, IFN-γ and TGF-β1, and protein expression levels of TNF receptor-associated factor 6, phosphorylated-p65 NF-κB, cleaved caspase-3 and cleaved caspase-9 in lung and intestinal tissue samples were downregulated in I/R-miR-146a-overexpressing mice, compared with those from the I/R-negative control group. Thus, the present study identified that pre-treatment with the miR-146a overexpression vector alleviated intestinal I/R-induced acute lung injury in mice.
Insights
MicroRNAs (miRs), specifically miR-146a, are crucial in intestinal injury. Overexpressing miR-146a in mice significantly reduced acute lung injury caused by intestinal ischemia/reperfusion (I/R).
Area of Science:
- Physiology
- Molecular Biology
- Pathology
Background:
- MicroRNAs (miRs) are implicated in intestinal ischemia/reperfusion (I/R) injury.
- The specific role of miR-146a in intestinal I/R-induced acute lung injury remains unclear.
Purpose of the Study:
- To investigate the role of miR-146a in intestinal I/R-induced acute lung injury.
- To determine if miR-146a overexpression can alleviate this condition.
Main Methods:
- An intestinal I/R mouse model was established.
- miR-146a expression was quantified using RT-qPCR.
- Histopathological changes were assessed via H&E staining.
- mRNA and protein levels of key inflammatory and apoptotic markers were measured using RT-qPCR and Western blotting.
Main Results:
- miR-146a expression was significantly downregulated in both intestinal and lung tissues following I/R injury.
- Overexpression of miR-146a alleviated lung and intestinal histopathological damage and pulmonary edema.
- Key inflammatory mediators (TNF-α, IL-1β, IFN-γ, TGF-β1) and apoptotic pathway proteins were downregulated in miR-146a overexpressing mice.
Conclusions:
- miR-146a plays a protective role against intestinal I/R-induced acute lung injury.
- Pre-treatment with a miR-146a overexpression vector is a potential therapeutic strategy for mitigating I/R-induced lung injury.

