期刊
TRANSPLANTATION
卷 105, 期 3, 页码 529-539出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0000000000003435
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The study demonstrates that miR-145 is upregulated in lung ischemia/reperfusion injury, enhancing autophagy processes and exacerbating the severity of lung damage.
Background. MicroRNA-145 (miR-145) has been shown to play a critical role in ischemia/reperfusion (I/R) injury; however, the expression and function of miR-145 in lung I/R injury have not been reported yet. This study aimed to elucidate the potential effects of miR-145 in lung I/R injury. Methods. Lung I/R mice models and hypoxia/reoxygenation (H/R) pulmonary microvascular endothelial cell models were established. The expression of miR-145 and sirtuin 1 (SIRT1) was measured with reverse transcription-quantitative polymerase chain reaction and Western blot analysis in mouse lung tissue and cells. Artificial modulation of miR-145 and SIRT1 (downregulation) was done in I/R mice and H/R cells. Additionally, Pao(2)/FiO(2) ratio, wet weight-to-dry weight ratio, and cell apoptosis in mouse lung tissues were determined by blood gas analyzer, electronic balance, and deoxyuridine triphosphate-biotin nick end-labeling assay, respectively. Autophagy marker Beclin 1 and LC3 expression, NF-kappa B acetylation levels, and autophagy bodies were detected in cell H/R and mouse I/R models by Western blot analysis. pulmonary microvascular endothelial cell apoptosis was detected with flow cytometry. Results. miR-145 was abundantly expressed in the lung tissue of mice and PMVECs following I/R injury. In addition, miR-145 directly targeted SIRT1, which led to significantly decreased Pao(2)/FiO(2) ratio and increased wet weight-to-dry weight ratio, elevated acetylation levels and transcriptional activity of NF-kappa B, upregulated expressions of tumor necrosis factor-alpha, interleukins-6, and Beclin 1, autophagy bodies, cell apoptosis, as well as LC3-II/LC3I ratio. Conclusions. In summary, miR-145 enhances autophagy and aggravates lung I/R injury by promoting NF-kappa B transcriptional activity via SIRT1 expression.
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