The human alpha11 integrin promoter drives fibroblast-restricted expression in vivo and is regulated by TGF-beta1 in a Smad- and Sp1-dependent manner

Matrix Biology : Journal of the International Society for Matrix Biology
Ning LuD Gullberg

Abstract

Integrin alpha11beta1 is expressed by ectomesenchymally- and mesodermally-derived fibroblasts and is the major collagen receptor on embryonic fibroblasts. We have previously characterized a 3kb human alpha11 promoter region in vitro. In the current study we generated promoter-LacZ reporter transgenic mice to examine the ability of the 3kb alpha11 promoter to drive tissue-specific expression also in vivo. Our data show that the 3 kb alpha11 promoter contains most of the regulatory elements that direct ectomesenchymal and mesodermal fibroblast-specific expression. Not much is known about integrin alpha11 regulation by TGF-beta family members and the potential role of alpha11 in TGF-beta1 driven processes such as fibrosis and wound contraction. In the current study we show that TGF-beta1 induces alpha11 transcription in the fibrosarcoma cell line HT1080 as well as in primary fibroblasts. Co-transfection of an expression plasmid encoding constitutively active ALK5 together with alpha11 promoter-luciferase reporter constructs demonstrated that TGF-beta1 responsive elements are located within the 3kb alpha11 promoter. Serial deletions located TGF-beta1 responsiveness to the proximal promoter (nt -176/+25) as well as to the region ext...Continue Reading

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Citations

Apr 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Roya NavabMing-Sound Tsao
Sep 26, 2015·Journal of Cellular Biochemistry·Alexandra GrellaTanja Dominko
Nov 18, 2017·Experimental & Molecular Medicine·Ruchi BansalJai Prakash
Feb 10, 2016·Journal of Cell Science·Cédric Zeltz, Donald Gullberg
Jun 26, 2014·Journal of Cellular Physiology·Ilana Talior-VolodarskyChristopher A McCulloch
Feb 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jonas SchnittertJai Prakash
Dec 22, 2016·Mediators of Inflammation·Ruchi BansalJai Prakash
Jan 13, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Paul JaraAnnie Pardo
Dec 12, 2020·Cell and Tissue Research·Jarkko KoivunenTaina Pihlajaniemi

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