Peroxisome proliferator-activated receptor-γ enhances human pulmonary artery smooth muscle cell apoptosis through microRNA-21 and programmed cell death 4

• DOI: 10.1152/ajplung.00532.2016
• Publication Date: 2017-05-18T20:25:19Z
• Authors: David E. Green; Tamara C. Murphy; Bum-Yong Kang; Brahmchetna Bedi; Zhihong Yuan; Ruxana T. Sadikot; C. Michael Hart
• Keywords: Hypoxia

Pulmonary hypertension (PH) is a progressive disorder whose cellular pathogenesis involves enhanced smooth muscle cell (SMC) proliferation and resistance to apoptosis signals. Existing evidence demonstrates that the tumor suppressor programmed death 4 (PDCD4) affects patterns of growth repair responses in systemic vasculature following experimental injury. In current study, regulation PDCD4 its functional effects on susceptibility pulmonary artery cells were explored. We previously demonstrated pharmacological activation nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) attenuated hypoxia-induced human (HPASMCs) by inhibiting expression mitogenic functions microRNA-21 (miR-21). we hypothesize PPARγ stimulates HPASMC miR-21. Our findings demonstrate reduced mouse lung upon exposure chronic hypoxia (10% O2 for 3 wk) hypoxia-exposed HPASMCs (1% O2). was hypoxia, miR-21 overexpression, or siRNA-mediated depletion. Activation inhibited resultant proliferation, while restoring levels baseline. Additionally, with rosiglitazone protein dose-dependent manner as increased annexin V detection flow cytometry. Collectively, these confers growth-inhibitory signals through suppression accompanying derepression augments undergo apoptosis.