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TGF-β stimulates biglycan synthesis via p38 and ERK phosphorylation of the linker region of Smad2

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Abstract

Transforming growth factor (TGF)-β treatment of human vascular smooth-muscle cells increases the expression of biglycan and causes marked elongation of its glycosaminoglycan (GAG) chains. We investigated the role of MAP kinases and Smad transcription factors in this response. TGF-β-stimulated phosphorylation of p38, ERK, and JNK as well as Smad2 at both its carboxy terminal (phospho-Smad2C) and in the linker region (phospho-Smad2L). Pharmacological inhibition of ERK and p38 blocked TGF-β-mediated GAG elongation and expression of biglycan whereas inhibition of JNK had no effect. Inhibition of ERK and p38 but not JNK attenuated the effect of TGF-β to increase phospho-Smad2L. High levels of phospho-Smad2L were detected in a nuclear fraction of TGF-β treated cells. Thus, MAP kinase signaling through ERK and p38 and via phosphorylation of the linker region of Smad2 mediates the effects of TGF-β on biglycan synthesis in vascular smooth-muscle cells.

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Acknowledgments

This work was supported by research grants from the National Health and Medical Research Council of Australia Project Grants (#268928 and #472611) and Development Grant #418934) (PJL), project grant from the Diabetes Australia Research Trust (NO) and a Grant-in-Aid from the National Heart Foundation of Australia (PJL). The PhD Program of MLB generously received support through a National Heart Foundation of Australia post-graduate scholarship and a post-graduate supervisor award from GlaxoSmithKline Australia.

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Correspondence to Peter J. Little.

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M. L. Burch and S. N. Y. Yang contributed equally to this work.

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Burch, M.L., Yang, S.N.Y., Ballinger, M.L. et al. TGF-β stimulates biglycan synthesis via p38 and ERK phosphorylation of the linker region of Smad2. Cell. Mol. Life Sci. 67, 2077–2090 (2010). https://doi.org/10.1007/s00018-010-0315-9

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  • DOI: https://doi.org/10.1007/s00018-010-0315-9

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