The Journal of Practical Medicine >

2023 , Vol. 39 >Issue 17: 2190 - 2195

DOI: https://doi.org/10.3969/j.issn.1006-5725.2023.17.007

Basic Research

Up⁃regulated miR⁃106b⁃5p in exosomes derived from pulmonary artery smooth muscle cells enhances Warburg effect of pulmonary artery endothelial cells and promotes arterial pulmonary hypertension

  • Ailifeire MAIMAITI ,
  • Jing GAO ,
  • Zixiang YU ,
  • Yitong. MA
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  • Department of Coronary Heart Disease，the First Affiliated Hospital，Xinjiang Medical University，Urumqi 830054，China

Received date: 2023-04-21

  Online published: 2023-09-27

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Abstract

Objective To explore the mechanisms of inter-cellular communication between pulmonary artery smooth muscle cells and pulmonary artery endothelial cells in promoting the progression of arterial pulmonary hypertension （PAH）. Methods Exosomes in peripheral blood of healthy individuals （HC） and PAH patients were collected and isolated， and miRNAs in the exosomes were determined by microarray and differential expression analysis. Primary human pulmonary artery smooth muscle cells （hPASMCs） and primary human pulmonary artery endothelial cells （hPAECs） were treated with normoxia or hypoxia in vitro. Bioinformatics analysis was performed to detect sequence interaction sites between miR-106b-5p and USP32. Adenovirus was transinfectedinto the hPASMCs of over-expressed/knocked-down miR-106b-5p， or into the hPAECs of the over-expressed/knocked-down of PKM2. Dual luciferase reporter assay was used for confirming the sequence interaction of miR-106b-5p and USP32. The levels of USP32， PKM2， GLUT1， HK2 and LDHA were determined by Western blot. Results By microarray assay and differential expression analysis， the level of miR-106b-5p in the peripheral blood-derived exosomes was significantly up-regulated in the PAH group as compared with HC group. Compared with normoxia group cells， the level of miR-106b-5p was significantly up-regulated in the hypoxia-induced hPASMCs cells’ supernatant exomsomes， but not in the exosomes of hPAECs cells’ supernatant. MiR-106b-5p negatively regulated the expression of USP32. Compared with the miR-NC group/inhibitor-NC group，the expressions of PKM2， GLUT1， HK2 and LDHA were significantly enhanced/inhibited after miR-106b-5p mimic/miR-106b-5p inhibitor was treated with hPASMCs. Compared with shRNA-NT/vector group， PKM2 shRNA/PKM2-OE treatment in hPAECs significantly inhibited/enhanced intracellular expressions of PKM2， GLUT1， HK2， and LDHA （P<0.05）. Conclusion HPASMCs enhances intracellular Warburg effect of hPAECs through up-regulating miR-106b-5p in exosomes， which has a potential role in promoting disease progression in arterial pulmonary hypertension.

Key words： arterial pulmonary hypertension; pulmonary smooth muscle cells; pulmonary endothelial cells; exosomes; miR-106b-5p; Warburg effect

Cite this article

Ailifeire MAIMAITI , Jing GAO , Zixiang YU , Yitong. MA . Up⁃regulated miR⁃106b⁃5p in exosomes derived from pulmonary artery smooth muscle cells enhances Warburg effect of pulmonary artery endothelial cells and promotes arterial pulmonary hypertension[J]. The Journal of Practical Medicine, 2023 , 39(17) : 2190 -2195 . DOI: 10.3969/j.issn.1006-5725.2023.17.007

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