In:
Transplantation, Ovid Technologies (Wolters Kluwer Health), Vol. 105, No. 3 ( 2021-03), p. 529-539
Abstract:
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, Pa o 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-κB 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 Pa o 2 /FiO 2 ratio and increased wet weight-to-dry weight ratio, elevated acetylation levels and transcriptional activity of NF-κB, upregulated expressions of tumor necrosis factor-α, 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-κB transcriptional activity via SIRT1 expression.
Type of Medium:
Online Resource
ISSN:
0041-1337
DOI:
10.1097/TP.0000000000003435
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2021
detail.hit.zdb_id:
2035395-9
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