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Open Access Research article

Decreased catalytic function with altered sumoylation of DNA topoisomerase I in the nuclei of scleroderma fibroblasts

Xiaodong Zhou1*, Wei Lin1, Filemon K Tan1, Shervin Assassi1, Mavin J Fritzler2, Xinjian Guo1, Roozbeh Sharif1, Tom Xia3, Syeling Lai4 and Frank C Arnett1

Author Affiliations

1 Division of Rheumatology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA

2 Department of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada

3 Rice University, Houston, Post Office Box 1892, TX 77030, USA

4 Departmant of Pathology, Baylor College of Medicine, Houston, TX 77030, USA

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Arthritis Research & Therapy 2011, 13:R128  doi:10.1186/ar3435

Published: 9 August 2011

Abstract

Introduction

Sumoylation is involved in nucleolus-nucleoplasm transport of DNA topoisomerase I (topo I), which may associate with changes of cellular and topo I functions. Skin fibroblasts of patients with systemic sclerosis (SSc) exhibit profibrotic cellular changes. The aims of this study were to examine the catalytic function and sumoylation of topo I in the nuclei of SSc fibroblasts, a major cell type involved in the fibrotic process.

Methods

Eleven pairs of fibroblast strains obtained from nonlesional skin biopsies of SSc patients and age/sex/ethnicity-matched normal controls were examined for catalytic function of nuclear topo I. Immunoprecipitation (IP)-Western blots were used to examine sumoylation of fibroblast topo I. Real-time quantitative RT-PCR was used to measure transcript levels of SUMO1 and COL1A2 in the fibroblasts.

Results

Topo I in nuclear extracts of SSc fibroblasts generally showed a significantly lower efficiency than that of normal fibroblasts in relaxing equivalent amounts of supercoiled DNA. Increased sumoylation of topo I was clearly observed in 7 of 11 SSc fibroblast strains. Inhibition of SUMO1 with SUMO1 siRNA improved the catalytic efficiency of topo I in the SSc fibroblasts. In contrast, sumoylation of recombinant topo I proteins reduced their catalytic function.

Conclusions

The catalytic function of topo I was decreased in SSc fibroblasts, to which increased sumoylation of topo I may contribute.