Role of miR‐21‐5p/FilGAP axis in estradiol alleviating the progression of monocrotaline‐induced pulmonary hypertension

Abstract

Background: Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH.Methods: Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline-induced PH (MCT-PH) male rats were treated with 17β-estradiol (E 2 ) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA.Results: Many circulating miRNAs, including miR-21-5p and miR-574-5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR-21-5p in the lungs was significantly upregulated in MCT-PH rats compared with the controls. However, miR-574-5p showed no difference in the lungs of MCT-PH rats and controls. miR-21-5p was selected for further analysis in rats as E 2 strongly regulated it. E 2 decreased miR-21-5p expression in the lungs of MCT-PH rats by ERβ. E 2 reversed miR-21-5p target gene FilGAP downregulation in the lungs of MCT-PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c-Jun in the lungs of MCT-PH rats was inhibited by E 2 and miR-21-5p antagonist.Conclusions: miR-21-5p level was remarkably associated with PH severity in patients.Moreover, the miR-21-5p/FilGAP signaling pathway modulated the protective effect of E 2 on MCT-PH through ERβ.

MiR-1249 on Endothelial Extracellular Vesicles Mediates Cigarette Smoke–Induced Pulmonary Hypertension by Inhibiting HDAC10 (Histone Deacetylase 10)-NFκB (Nuclear Factor κB)-CaSR (Calcium-Sensing Receptor) Cascade

“…However, growing evidences show that the smoking-induced PH may be associated with distinct miRNAs profile than in PA hypertension. [44][45][46] The smoking-induced spermine enrichment in eEVs demonstrated in our previous work 9 probably affects miR-1249 generation because the inhibition of spermine production attenuated the induction of miR-1249 expression (Figure S6). In addition, pulmonary endothelium, but not the heart or liver, maybe the primary source of miR-1249 eEVs generation (Figure S2).…”

Expression and prognosis of inducible T‐cell co‐stimulator and its ligand in Chinese stage I–III lung adenocarcinoma patients

“…Kaplan-Meier method was used to draw the survival curve. 14 The rank-sum test and χ 2 test were used for intergroup comparison.…”

Circulating cervical cancer biomarkers potentially useful in medical attention (Review)

“…Most information is related to protein biomarkers and some of them were regulated by estrogens in tissues: SCC-Ag, C-125, VEGFA and ACTN4, and only circulating HMGB1 and YKL-40 were regulated by estrogens (77)(78)(79)(80)(81). Notably, the circulating miR-21 expression was downregulated by estrogens (82).…”

“…cDNA was discovered several years ago ( 82 ) and its relationship with cancer was later identified ( 83 ). The total cDNA concentration is considerably lower in healthy individuals than in patients with cancer ( 84 ) and it varies depending on the cancer type ( 85 ).…”