Arginase II is a target of miR-17-5p and regulates miR-17-5p expression in human pulmonary artery smooth muscle cells

作者：Jin Youpeng; Jin Yi; Chen Bernadette; Tipple Trent E; Nelin Leif D^*

来源：American Journal of Physiology - Lung Cellular and Molecular Physiology, 2014, 307(2): L197-L204.

DOI：10.1152/ajplung.00266.2013

• hypoxia
• pulmonary hypertension
• pulmonary vascular remodeling

Vascular remodeling and smooth muscle cell proliferation are hallmark pathogenic features of pulmonary artery hypertension. MicroRNAs, endogenously expressed small noncoding RNAs, regulate gene expression at the posttranscriptional level. It has previously been shown that miR-17 overexpression in cultured human pulmonary artery smooth muscle cell (hPASMC) resulted in increased viable cell number. Previously, we have found that arginase II promotes hypoxia-induced proliferation in hPASMC. Therefore, we hypothesized that miR-17 would be upregulated by hypoxia in hPASMC and would result in greater arginase II expression. We found that levels of miR-17-5p and arginase II were significantly greater in cultured hPASMC exposed to 1% O-2 for 48 h than in hPASMC exposed to 21% O-2 for 48 h. Furthermore, inhibiting miR-17-5p expression decreased hypoxia-induced arginase II protein levels in hPASMC. Conversely, overexpressing miR-17-5p resulted in greater arginase II protein levels. Somewhat surprisingly, arginase II inhibition was associated with lower miR-17-5p expression in both normoxic and hypoxic hPASMC, whereas overexpressing arginase II resulted in greater miR-17-5p expression in hPASMC. These findings suggest that hypoxia-induced arginase II expression is not only regulated by miR-17-5p but also that there is a feedback loop between arginase II and miR-17-5p in hPASMC. We also found that the arginase II-mediated regulation of miR-17-5p was independent of either p53 or c-myc. We also found that L-arginine, the substrate for arginase II, and L-ornithine, the amino acid product of arginase II, were not involved in the regulation of miR-17-5p expression.

• 出版日期2014-7-15
• 单位山东大学