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

American Journal of Physiology. Lung Cellular and Molecular Physiology
David E GreenC Michael Hart

Abstract

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 cell death 4 (PDCD4) affects patterns of cell growth and repair responses in the systemic vasculature following experimental injury. In the current study, the regulation PDCD4 and its functional effects on growth and apoptosis susceptibility in pulmonary artery smooth muscle cells were explored. We previously demonstrated that pharmacological activation of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) attenuated hypoxia-induced proliferation of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting the expression and mitogenic functions of microRNA-21 (miR-21). In the current study, we hypothesize that PPARγ stimulates PDCD4 expression and HPASMC apoptosis by inhibiting miR-21. Our findings demonstrate that PDCD4 is reduced in the mouse lung upon exposure to chronic hypoxia (10% O2 for 3 wk) and in hypoxia-exposed HPASMCs (1% O2). HPASMC apoptosis was reduced by hypoxia, by miR-21 overexpression, or by siRNA-mediated PPARγ and PDCD4 depl...Continue Reading

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Citations

Nov 29, 2017·American Journal of Respiratory Cell and Molecular Biology·Samantha M YeligarC Michael Hart
Feb 20, 2019·International Journal of Molecular Sciences·Lei FangMichael Roth
Aug 17, 2019·Scientific Reports·Nicholas M MauriceRuxana T Sadikot
Nov 22, 2019·Journal of Cellular and Molecular Medicine·Xuguang LiFang Wang
Oct 3, 2019·American Journal of Respiratory Cell and Molecular Biology·Georg HansmannStephen Y Chan
Feb 5, 2019·Experimental Biology and Medicine·Gexiang CaiXiaoying Huang
Oct 30, 2018·Nucleic Acids Research·Zhan TongYuan Zhou
Dec 26, 2018·Antioxidants & Redox Signaling·Victor TsengC Michael Hart
Oct 10, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Ettore LignelliRory E Morty
Jan 29, 2021·International Journal of Molecular Sciences·Nabham RaiTatyana Novoyatleva
Jan 7, 2022·Journal of Cellular and Molecular Medicine·Meibin WangXiaoying Huang

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Methods Mentioned

BETA
transfection
transfections
Assay
fluorescence-activated cell sorting
PCR
ELISA
FACS

Software Mentioned

FACSDiva
Cor
Graphpad Prism
Li
GraphPad

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis