MicroRNA‑30a‑5p promotes proliferation and inhibits apoptosis of human pulmonary artery endothelial cells under hypoxia by targeting YKL‑40

Tan, Hong Kee; Yao, Hua; Lie, Zhenbang; Guo, Chenchen; Lin, Shu; Zhang, Ying

doi:10.3892/mmr.2019.10251

Cited by 12 publications

(12 citation statements)

References 30 publications

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“…The inhibition of miR-335-3p resulted in the attenuation of chronic normobaric hypoxia-induced vascular remodeling and PAH in mice [91]. A significant increase in miR-30a-5p level in the plasma of PAH patients was recently reported [92]. Hypoxia exposure to HPAECs progressively downregulated miR-30a-5p and upregulated YKL-40 levels in a time-dependent manner.…”

Section: Pahmentioning

confidence: 83%

“…For example, miR-27a-3p attenuated pulmonary fibrosis, and in another report, miR-27a supported PAH [73,90]. Similarly, miR-30a interrupted the development of asthma, and on the other hand, miR-30a-5p promoted PAH [63,92]. miR-29a and miR-29c inhibited the pathogenesis of IPF, and miR-29b regulated inflammation in COPD [47,77,79,80].…”

Section: Comparative Role Of Mirnas In Lung Development and Diseasesmentioning

confidence: 93%

“…To investigate the functional role of the miRNA, HPAECs were exposed to hypoxia after transfection with miR-30a-5p mimic. Consequently, miR-30a-5p enhanced the proliferation and attenuated the apoptosis of HPAECs [92]. Figure 2 shows a summary of miRNAs involved in pulmonary arterial hypertension and the other lung diseases discussed.…”

Section: Pahmentioning

confidence: 99%

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miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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The development of the lung involves a diverse group of molecules that regulate cellular processes, organ formation, and maturation. The various stages of lung development are marked by accumulation of small RNAs that promote or repress underlying mechanisms, depending on the physiological environment in utero and postnatally. To some extent, the pathogenesis of various lung diseases is regulated by small RNAs. In this review, we discussed miRNAs regulation of lung development and diseases, that is, COPD, asthma, pulmonary fibrosis, and pulmonary arterial hypertension, and also highlighted possible connotations for human lung health.After fertilization in the mouse, total miRNA in the two-cell-stage embryo was demonstrated to be significantly lower than the levels in one-cell zygote [15]. Notably, total miRNA in the four-cell-stage embryo was higher than the levels in the two-cell-stage embryo [15]. In the early mouse embryo, miR-127 was upregulated at E6.5 and E7.5 [16]. Overexpression of miR-127 in mouse embryonic stem cells, which differentiated into embryoid bodies, increased the mRNA levels of Gsc, Foxa2, and Brachyury (mesendoderm markers), but elicited no change in Pax6 and Otx2 (ectoderm markers) three days after transfection. Inhibition of miR-127 showed opposite regulation of Gsc, Foxa2, and Brachyury. miR-127, moreover, was suggested to control mesendoderm differentiation [16]. miR-326 regulated sonic hedgehog signaling by targeting Smo and Gli2 [17]. The inhibition of smoothened in cultured explanted E12 mouse lung resulted in the expansion of distal epithelium, and disruption of normal branching pattern and mesenchymal integrity [17]. Another study described the functional role of miR-142-3p in the mouse embryonic lung mesenchyme. The miRNA was shown to regulate adenomatous polyposis coli to further modulate Wnt signaling [18]. Taken together, miR-142-3p regulated the proliferation and differentiation of mesenchymal progenitors in the mouse embryonic lung [18].In the developing mouse lung, the level of miR-17 was stable (E11.5-E16.5), predominantly at the pseudoglandular stage, with higher epithelial levels at E12.5 [19]. Simultaneous knockdown of miR-17 and its paralogs, miR-20a and miR-106b, for 72 h in epithelial lung explants altered branching, even in FGF10-treated condition [19]. In the human fetal lung, miR-449a was upregulated at 18-20 weeks (canalicular stage), and in the mouse embryonic lung, miR-449a level was increased from E15.5 to E18.5 [20]. The inhibition of miR-449a in E16.5 mouse lung culture (end of pseudoglandular stage) increased the mRNA levels of Mycn and Sox9, and the protein levels of Ki-67 and SOX9 particularly in the distal epithelial region [20].Knockout of miR-26a-1/miR-26a-2 in the mouse promoted the formation of dilated lumens and aerated regions at the beginning of the canalicular stage (E16.5) of lung development [21]. Results at the saccular stage (E18.5) also indicated large lamellar bodies, and increased SP-A, SP-B, and SP-C protein levels in miR-26a knockout mice....

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Section: Pahmentioning

confidence: 83%

Section: Comparative Role Of Mirnas In Lung Development and Diseasesmentioning

confidence: 93%

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miRNAs in Lung Development and Diseases

Boateng

Krauss‐Etschmann

2020

IJMS

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“…Total cellular protein extraction, protein concentration quantification and western blotting were performed as described in our previous report [20]. Briefly, proteins were transferred onto a polyvinylidene difluoride (PVDF) membrane after separation using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).…”

Section: Western Blottingmentioning

confidence: 99%

Upregulation of miR-361-3p suppresses serotonin-induced proliferation in human pulmonary artery smooth muscle cells by targeting SERT

et al. 2020

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Background Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is a key mechanism in pulmonary arterial hypertension (PAH). Serotonin (5-hydroxytryptamine, 5-HT) can induce abnormal proliferation of PASMCs. The role of miR-361-3p in serotonin-induced abnormal PASMCs proliferation remains unclear. Methods The miR-361-3p level was analyzed in plasma from PAH patients and normal controls and in human PASMCs (hPASMCs) using RT-PCR. The hPASMCs were transfected with an miR-361-3p mimic and then treated with serotonin. Untransfected hPASMCs were used as the control. Cell proliferation was evaluated using an MTS assay and 5-ethynyl-2′-deoxyuridine (EdU) staining. The cell cycle stages were evaluated using flow cytometry. The association between miR-361-3p and serotonin transporter (SERT) was determined using a luciferase reporter assay and anti-AGO2 RNA immunoprecipitation assay. The protein expression was evaluated via western blotting. Results The miR-361-3p level was lower in plasma from PAH patients than in plasma from the any of the normal control subjects. The mean pulmonary arterial pressure, pulmonary vascular resistance and pulmonary vascular resistance index were higher in PAH patients whose miR-361-3p level was lower than the median value for patients than in those whose miR-361-3p level was higher than the median. Serotonin treatment reduced miR-361-3p expression in the hPASMCs. MiR-361-3p overexpression suppressed cell proliferation, promoted apoptosis, induced G1 arrest, and decreased the phosphorylation level of ERK1/2 in serotonin-treated hPASMCs. SERT was identified as an miR-361-3p target. Its overexpression alleviated the effect of miR-361-3p overexpression on serotonin-induced hPASMC proliferation and upregulation of phosphorylated ERK1/2. Conclusions The miR-361-3p level is lower in the plasma of PAH patients. Upregulation of miR-361-3p suppresses serotonin-induced proliferation of hPASMCs by targeting SERT. Our results suggest that miR-361-3p is a potential therapeutic target in PAH.

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“…MicroRNAs (miRNAs or miRs) are a conserved class of small non-coding RNAs that can regulate gene expression at the post-transcriptional level (10). Recent studies have indicated that abundant miRNAs participate in the pathogenesis of PAH (11)(12)(13)(14). miR-27b has been shown to suppress endothelial cell proliferation and migration in Kawasaki disease (15).…”

Section: Introductionmentioning

confidence: 99%