Ox-LDL-induced TGF-β1 production in human alveolar epithelial cells: involvement of the Ras/ERK/PLTP pathway.

Abstract:

:Oxidized-low density lipoprotein (Ox-LDL) has been shown to play an important role in impaired surfactant metabolism and transforming growth factor-β1 (TGF-β1) is a critical mediator in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). In this study, we investigated whether Ox-LDL can induce TGF-β1 protein production, and if so, how it achieves this induction in human alveolar epithelial cells (A549). We show here that Ox-LDL not only caused a dose- and time-dependent up-regulation of TGF-β1 production, but also increased Smad3 phosphorylation, Ras/extracellular signal-regulated kinase (ERK) activity and phospholipid transfer protein (PLTP) expression in A549 cells. The inhibition of Ras/ERK activity with specific inhibitors significantly suppressed Ox-LDL-induced TGF-β1 production, Smad3 phosphorylation and PLTP expression. Furthermore, treatment of cells with PLTP siRNA suppressed both TGF-β1 release and Smad3 activation induced by Ox-LDL, but not the activation of Ras/ERK cascade. Taken together, we provide evidences that induction of TGF-β1 production and Smad3 phosphorylation by Ox-LDL is mediated by Ras/ERK/PLTP pathway in human alveolar epithelial cells.

journal_name

J Cell Physiol

authors

Guo LL,Chen YJ,Wang T,An J,Wang CN,Shen YC,Yang T,Zhao L,Zuo QN,Zhang XH,Xu D,Wen FQ

doi

10.1002/jcp.24005

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

3185-91

issue

9

eissn

0021-9541

issn

1097-4652

journal_volume

227

pub_type

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