![]() There is no direct evidence indicating pathogenic roles of the antibodies. A causal contribution of anti-topo I to the SSc phenotype is still unclear. Anti-DNA topoisomerase I (topo I) autoantibody is one of the disease-specific autoantibodies, and it occurs in 15 to 25% of patients. The majority of SSc patients (95%) have autoantibodies against various nuclear, nucleolar and cytoplasmic proteins, which include non-specific antinuclear antibodies (ANA) and a number of disease specific autoantibodies. It is believed that a possible defect in regulation of biological functions is present in SSc fibroblasts. Skin fibroblasts obtained from SSc patients have been found to be profibrotic and to synthesize excessive amounts of ECM proteins, which contribute to tissue fibrosis. The latter subset is characterized by more rapid progression of skin and visceral involvement, as well as poorer prognosis. Cutaneous fibrosis is a common clinical presentation and, based on the extent of skin involvement, SSc is classified into limited and diffuse cutaneous forms. ![]() Systemic sclerosis (SSc) is a human multi-system fibrotic disease with high morbidity and mortality but the etiology is largely unknown and the pathogenesis has yet to be clearly elucidated. The catalytic function of topo I was decreased in SSc fibroblasts, to which increased sumoylation of topo I may contribute. ![]() In contrast, sumoylation of recombinant topo I proteins reduced their catalytic function. Inhibition of SUMO1 with SUMO1 siRNA improved the catalytic efficiency of topo I in the SSc fibroblasts. Increased sumoylation of topo I was clearly observed in 7 of 11 SSc fibroblast strains. 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. Real-time quantitative RT-PCR was used to measure transcript levels of SUMO1 and COL1A2 in the fibroblasts. Immunoprecipitation (IP)-Western blots were used to examine sumoylation of fibroblast topo I. MethodsĮleven 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. 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. Skin fibroblasts of patients with systemic sclerosis (SSc) exhibit profibrotic cellular changes. Sumoylation is involved in nucleolus-nucleoplasm transport of DNA topoisomerase I (topo I), which may associate with changes of cellular and topo I functions.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |