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Crosstalk between Smad2/3 and specific isoforms of ERK in TGF-β1-induced TIMP-3 expression in rat chondrocytes.

Crosstalk between Smad2/3 and specific isoforms of ERK in TGF-β1-induced TIMP-3 expression in rat chondrocytes.
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Zhu Y, Gu J, Zhu T, Jin C, Hu X, Wang X,


Zhu Y, Gu J, Zhu T, Jin C, Hu X, Wang X, (click to view)

Zhu Y, Gu J, Zhu T, Jin C, Hu X, Wang X,

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Journal of cellular and molecular medicine 2017 02 23() doi 10.1111/jcmm.13099
Abstract

This study investigated the roles of ERK1 and ERK2 in transforming growth factor-β1 (TGF-β1)-induced tissue inhibitor of metalloproteinases-3 (TIMP-3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF-β1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF-β1. At indicated time-points, TIMP-3 expression was determined by real-time PCR and Western blotting; p-Smad3, nuclear p-Smad3, Smad2/3, p-ERK1/2 and ERK1/2 levels were assessed. And then, aggrecan, type II collagen and the intensity of matrix were examined. TGF-β1-induced TIMP-3 expression was significantly inhibited by ERK1 knock-down, and the decrease in TIMP-3 expression was accompanied by a reduction of p-Smad3 in ERK1 knock-down cells. Knock-down of ERK2 had no effect on neither TGF-β1-induced TIMP-3 expression nor the quantity of p-Smad3. Moreover, aggrecan, type II collagen expression and the intensity of matrix were significantly suppressed by ERK1 knock-down instead of ERK2 knock-down. Taken together, ERK1 and ERK2 have different roles in TGF-β1-induced TIMP-3 expression in rat chondrocytes. ERK1 instead of ERK2 can regulate TGF-β/Smad signalling, which may be the mechanism through which ERK1 regulates TGF-β1-induced TIMP-3 expression.

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