MiR-135a inhibitor alleviates pulmonary arterial hypertension through β-Catenin/GSK-3β signaling pathway.

OBJECTIVE: The aim of this study was to investigate the regulatory role of micro-ribonucleic acid (miR)-135a in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats, and to analyze the possible regulatory mechanism. MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were randomly divided into three groups, including the blank control group, model group and miR-135a inhibitor intervention group. The right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI) were measured in rats of each group. Hematoxylin and eosin (HE) staining was adopted to detect the pathological changes in lung tissues of rats. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of interleukin-6 (IL-6) and IL-1 beta in lung tissues. Meanwhile, the messenger RNA (mRNA) and protein levels of beta-catenin and glycogen synthase kinase-3 beta (GSK-3 beta) in lung tissues of rats were determined via Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting assay, respectively. RESULTS: Compared with the blank control group, RVSP and RVHI increased significantly in the model group. The pathological morphology of the lung tissues was poor, and the content of IL-6 and IL-1 beta was markedly up-regulated in the model group. Meanwhile, the mRNA and protein levels of beta-catenin and GSK-3 beta were notably elevated in the model group than the blank control group. In the miR-135a inhibitor intervention group, RVSP and RVHI decreased significantly, and the pathological morphology of lung tissues was evidently improved when compared with the blank control group. Furthermore, the content of IL-6 and IL-1 beta was remarkably reduced, and the mRNA and protein levels of beta-catenin and GSK-3 beta were significantly declined in the miR-135a inhibitor intervention group. CONCLUSIONS: MiR-135a inhibitor significantly alleviates inflammatory response in the lung tissues and ameliorates damage to the pathological morphology. The possible underlying mechanism may be associated with the beta-catenin/GSK-3 beta signaling pathway.