Egr-1 mediates leptin-induced PPARγ reduction and proliferation of pulmonary artery smooth muscle cells

Xinming Xie, Shaojun Li, Yanting Zhu, Lu Liu, Rui Ke, Jian Wang, Xin Yan, Lan Yang, Li Gao, Weijin Zang, Manxiang Li

Research output: Contribution to journalArticlepeer-review

Abstract

Loss of peroxisome proliferator-activated receptor γ (PPARγ) has been found to contribute to pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary arterial remodeling therefore the development of pulmonary hypertension (PH). Yet, the molecular mechanisms underlying PPARγ reduction in PASMC remain poorly understood. Here, we demonstrated that leptin dose- and time-dependently inducued PPARγ down-regulation and proliferation of primary cultured rat PASMC, this was accompanied with the activation of extracellular regulated kinase1/2 (ERK1/2) signaling pathway and subsequent induction of early growth response-1 (Egr-1) expression. The presence of MEK inhibitors U0126 or PD98059, or prior silencing Egr-1 with small interfering RNA suppressed leptin-induced PPARγ reduction. In addition, activation of PPARγ by pioglitazone or targeting ERK1/2/Egr-1 suppressed leptin-induced PASMC proliferation. Taken together, our study indicates that ERK1/2 signaling pathway-mediated leptin-induced PPARγ reduction and PASMC proliferation through up-regulation of Egr-1 and suggests that targeting leptin/ERK1/2/Egr-1 pathway might have potential value in ameliorating vascular remodeling and benefit PH.

Original languageEnglish (US)
Pages (from-to)356-362
Number of pages7
JournalMolecular biology of the cell
Volume29
Issue number3
DOIs
StatePublished - Feb 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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