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Crosstalk between transforming growth factor-β1 and endoplasmic reticulum stress regulates alpha-smooth muscle cell actin expression in podocytes.

Abstract：

AIMS:Transforming growth factor-β1 (TGF-β1) plays a significant role in epithelial-mesenchymal transition (EMT). Furthermore, endoplasmic reticulum (ER) stress also can induce EMT. However, the relationship among TGF-β1, ER stress and EMT in podocytes is still unclear. Consequently, this study examines the crosstalk effect between TGF-β1 and ER stress on the regulation of EMT. MAIN METHODS:The mRNA of EMT marker (α-smooth muscle actin: α-SMA) was evaluated by quantitative real-time PCR. In addition, the protein expressions of α-SMA and three ER stress biomarkers (glucose-regulated protein 78: GRP78; eukaryotic translation initiation factor 2α: eIF2α; CCAAT/enhancer-binding protein-homologous protein: CHOP) were evaluated by Western blot. KEY FINDINGS:TGF-β1 increased the ER stress response biomarkers (GRP78, p-eIF2α/eIF2α and CHOP) and mRNA and protein levels of α-SMA in podocytes. Furthermore, ER stress inducer (thapsigargin) increased α-SMA protein expression. ER stress inhibitor (4-phenylbutyrate) attenuated the ER stress response and α-SMA protein expression under treatment with TGF-β1. Among the various TGF-β1 down-stream pathway inhibitors considered in the present study (SIS3: inhibitor of Smad2/3; U0126: inhibitor of MEK/ERK; SB203580: inhibitor of p38), SIS3 greatly attenuated the ER stress response biomarker (GRP78) under treatment with TGF-β1. SIS3, U0126 and SB203580 all partly attenuated α-SMA mRNA expression under TGF-β1 treatment. However, only SIS3 attenuated α-SMA protein expression. SIGNIFICANCE:The present results confirm that ER stress induces α-SMA protein expression in podocytes. Furthermore, TGF-β1 mainly regulates ER stress and α-SMA protein expression through the Smad2/3 pathway. Therefore, ER stress and TGF-β1 may synergistically induce podocytes to undergo EMT.

journal_name

Life Sci

journal_title

Life sciences

authors

Chen CA,Chang JM,Chang EE,Chen HC,Yang YL

doi

10.1016/j.lfs.2018.07.050

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

9-14

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(18)30436-3

journal_volume

209

pub_type

杂志文章

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Crosstalk between transforming growth factor-β1 and endoplasmic reticulum stress regulates alpha-smooth muscle cell actin expression in podocytes.