Polyphyllin VII alleviates pulmonary hypertension by inducing miR-205-5p to target the β-catenin pathway

Objective: This study aims to investigate the impact of Polyphyllin VII (PP7) on pulmonary hypertension (PH) and elucidate the underlying mechanism involving microRNA (miR)- 205-5p/beta-catenin.Methods: The PH rat model was induced through hypoxia exposure. The effects of intraperitoneal injection of PP7 on pulmonary artery tissue pathology, hemodynamics, miR-205-5p expression and beta-catenin protein levels were assessed. In vitro, pulmonary arterial smooth muscle cells (PASMCs) were subjected to hypoxic conditions. Moreover, miR-205-5p and/or beta-catenin were overexpressed through transfection. PASMCs were pre-cultured in 20 mu M PP7, and subsequent measurements included proliferation, apoptosis and vascular remodeling protein expression.Results: PP7 ameliorated PH symptoms in rats, upregulated miR-205-5p expression and inhibited beta-catenin protein expression. Furthermore, miR-205-5p upregulation inhibited beta-catenin expression in PASMCs. The overexpression of beta-catenin aggravated hypoxia-induced proliferation, inhibited apoptosis and further augmented VEGF and alpha-SMA protein expression. Additionally, miR-205-5p overexpression alleviated the hypoxia-induced PASMC proliferation and apoptosis by inhibiting beta-catenin protein expression. Under hypoxic conditions, PP7 significantly elevated miR-205-5p while downregulating beta-catenin protein expression. Furthermore, inhibiting miR-205-5p counteracted the inhibitory effect of PP7 on beta-catenin, consequently blocking the regulatory role of PP7 in PASMC proliferation and apoptosis.Conclusion: PP7 likely modulates beta-catenin protein levels by promoting miR-205-5p expression, thereby alleviating PH, vascular remodeling and airway smooth muscle remodeling.

Automated summary

The study reveals that PP7 modulates beta-catenin protein levels by promoting miR-205-5p expression, thereby alleviating PH symptoms and vascular remodeling. Furthermore, the overexpression of miR-205-5p can attenuate hypoxia-induced proliferation and apoptosis in pulmonary arterial smooth muscle cells (PASMCs), while the overexpression of beta-catenin exacerbates these effects.