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Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
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MiR-135a inhibitor alleviates pulmonary arterial hypertension through β-Catenin/GSK-3β signaling pathway

R-H Yu1, L-M Wang, X-H Hu

  • 1Department of Respiratory Medicine, Xuhui District Central Hospital, Shanghai, China. xhyyhxh@163.com.

European Review for Medical and Pharmacological Sciences
|November 28, 2019
PubMed
Abstract

Insights

Micro-ribonucleic acid (miR)-135a inhibition alleviates pulmonary arterial hypertension (PAH) in rats by reducing inflammation and improving lung tissue damage. This suggests a therapeutic role for miR-135a inhibitors in PAH treatment via the β-catenin/GSK-3β pathway.

Area of Science:

  • Molecular Biology
  • Cardiovascular Research
  • Pulmonary Hypertension

Background:

  • Pulmonary arterial hypertension (PAH) is a severe condition characterized by high blood pressure in the lung arteries.
  • Micro-ribonucleic acids (miRNAs) play crucial roles in regulating cellular processes, and their dysregulation is implicated in various diseases, including PAH.
  • The specific role of miR-135a in the pathogenesis of monocrotaline (MCT)-induced PAH requires further investigation.

Purpose of the Study:

  • To investigate the regulatory role of miR-135a in a rat model of MCT-induced pulmonary arterial hypertension (PAH).
  • To analyze the potential underlying molecular mechanism through which miR-135a influences PAH development.
  • To evaluate the therapeutic effect of a miR-135a inhibitor on established PAH.

Main Methods:

  • Establishment of a monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) rat model.
  • Administration of a miR-135a inhibitor to assess its therapeutic effects.
  • Measurement of right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI).
  • Histopathological examination of lung tissues using Hematoxylin and eosin (HE) staining.
  • Quantification of inflammatory markers (IL-6, IL-1β) via ELISA.
  • Determination of β-catenin and GSK-3β mRNA and protein levels using RT-PCR and Western blotting.

Main Results:

  • MCT induction led to significantly increased RVSP, RVHI, and pulmonary inflammation, evidenced by elevated IL-6 and IL-1β levels.
  • MCT-induced PAH rats exhibited upregulated mRNA and protein levels of β-catenin and GSK-3β in lung tissues.
  • Treatment with a miR-135a inhibitor markedly reduced RVSP, RVHI, and inflammatory markers, while improving lung tissue pathology.
  • The miR-135a inhibitor also significantly decreased the expression of β-catenin and GSK-3β.

Conclusions:

  • Micro-ribonucleic acid (miR)-135a inhibition demonstrates significant therapeutic potential in mitigating MCT-induced pulmonary arterial hypertension (PAH) in rats.
  • The inhibitory effect of miR-135a on PAH is associated with the alleviation of pulmonary inflammatory responses and improvement of lung tissue damage.
  • The underlying mechanism may involve the modulation of the β-catenin/GSK-3β signaling pathway.

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