Increased TG2 expression can result in induction of transforming growth factor β1, causing increased synthesis and deposition of matrix proteins, which can be regulated by nitric oxide

Abstract

In fibrotic conditions increases in TG2 activity has been linked to an increase in the deposition of extracellular matrix proteins. Using TG2 transfected Swiss 3T3 fibroblasts expressing TG2 under the control of the tetracycline-regulated inducible promoter, we demonstrate that induction of TG2 not only stimulates an increase in collagen and fibronectin deposition but also an increase in the expression of these proteins. Increased TG2 expression in these fibroblasts led to NF-kappaB activation, resulting in the increased expression of transforming growth factor (TGF) beta(1). In addition, cells overexpressing TG2 demonstrated an increase in biologically active TGFbeta(1) in the extracellular environment. A specific site-directed inhibitor of TG abolished the NF-kappaB and TGFbeta1 activation and the subsequent elevation in the synthesis and deposition of extracellular matrix proteins, confirming that this process depends on the induction of transglutaminase activity. Treatment of TG2-induced fibroblasts with nontoxic doses of nitric oxide donor S-nitroso-N-acetylpenicillamine resulted in decreased TG2 activity and apprehension of the inactive enzyme on the cell surface. This was paralleled by a reduction in activation of NF-kappaB and TGFbeta(1) production with a subsequent decrease in collagen expression and deposition. These findings support a role for NO in the regulation of TG2 function in the extracellular environment.

Publication DOI: https://doi.org/10.1074/jbc.M109.041806
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Aston University (General)
Additional Information: This research was originally published in The Journal of biological chemistry. 2. Telci, Dilek; Collighan, Russell; Basaga, Huveyda and Griffin, Martin (2009) Increased TG2 expression can result in induction of transforming growth factor beta1, causing increased synthesis and deposition of matrix proteins, which can be regulated by nitric oxide. The Journal of biological chemistry. 2009; 284:29547-29558. © the American Society for Biochemistry and Molecular Biology
Uncontrolled Keywords: fibrotic conditions,TG2 activity,deposition,extracellular matrix proteins
Publication ISSN: 1083-351X
Last Modified: 13 Mar 2024 08:10
Date Deposited: 11 Mar 2019 17:55
Full Text Link: http://www.jbc. ... 7.full.pdf+html
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2009-10-23
Authors: Telci, Dilek
Collighan, Russell (ORCID Profile 0000-0003-0204-5125)
Basaga, Huveyda
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)

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