Knockdown of COL1A2 reduces hypoxia-induced over proliferation and oxidative stress in pulmonary artery smooth muscle cells by inhibiting TGF-beta signaling pathway

COL1A2 is implicated in hypoxia-induced changes in pulmonary artery smooth muscle cells; however, little is known about its role in treating these cells and the related mechanisms. We analyzed COL1A2 expression using RNA-seq data. GeneCards identified genes related to COL1A2 and PAH. STRING generated protein interaction networks. PASMCs served as the PAH in vitro model. Groups included control, si-NC, si-COL1A2, hypoxia, hypoxia + si-NC, hypoxia + si-COL1A2, and hypoxia + si-COL1A2 + SRI-011381. We assessed cell viability, proliferation, migration, invasion, apoptosis, MDA, and SOD levels. COL1A2 was identified as a key target gene associated with PAH. Hypoxia significantly increased COL1A2 expression in PASMCs, but si-COL1A2 effectively reduced its levels. Eight genes linked to both COL1A2 and PAH were enriched in the TGF-beta signaling pathway. Hypoxia increased the expression of TGFβ1 and Smad3, which were reversed by si-COL1A2 and subsequently restored by SRI-011381. Additionally, hypoxia-treated caused increases in cell viability, proliferation, migration, invasion, and MDA levels, and decreases in apoptosis and SOD levels in PASMCs. These effects were reversed by si-COL1A2 and restored by SRI-011381. Silencing COL1A2 can reduce cell viability, proliferation, migration, and invasion, while enhancing cell apoptosis and antioxidative responses to mitigate hypoxia-induced pulmonary arterial hypertension by inhibiting the TGF-beta signaling pathway.