Pharmacological activation of PPARγ inhibits hypoxia-induced proliferation through a caveolin-1 targeted and dependent mechanism in PASMCs

Previously, we and others have demonstrated that activation of peroxisome proliferator- activated receptor γ (PPARγ) by specific pharmacological agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH) by suppressing the proliferation and migration in distal pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial effects of PPARγ are mediated by targeting the intracellular calcium homeostasis and store-operated calcium channel (SOCC) proteins, including the main caveolae component caveolin-1. However, other than the caveolin-1 targeted mechanism, in this study, we further uncovered a caveolin-1 dependent mechanism within the activation of PPARγ by specific agonist GW1929. First, effective knockdown of caveolin-1 by small interfering RNA (siRNA) markedly abolished the upregulation of GW1929 on PPARγ expression at both mRNA and protein levels; Then, in HEK293T which is previously reported with low endogenous caveolin-1 expression, exogenous expression o...