Increased accumulation of extracellular thrombospondin-2 due to low degradation activity stimulates type I collagen expression in scleroderma fibroblasts.
| Autor: | Kajihara I; Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan., Jinnin M, Yamane K, Makino T, Honda N, Igata T, Masuguchi S, Fukushima S, Okamoto Y, Hasegawa M, Fujimoto M, Ihn H |
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| Jazyk: | angličtina |
| Zdroj: | The American journal of pathology [Am J Pathol] 2012 Feb; Vol. 180 (2), pp. 703-14. Date of Electronic Publication: 2011 Dec 03. |
| DOI: | 10.1016/j.ajpath.2011.10.030 |
| Abstrakt: | The aim of the present study was to determine the expression and role of thrombospondin-2 (TSP-2) in systemic sclerosis (SSc). Both TSP-2 mRNA levels and protein synthesis in cell lysates were significantly lower in cultured SSc fibroblasts than in normal fibroblasts; however, the TSP-2 protein that accumulated in the conditioned medium of SSc fibroblasts was up-regulated, compared with that of normal fibroblasts, because of an increase in the half-life of the protein. In vivo serum TSP-2 levels were higher in SSc patients than in healthy control subjects, and SSc patients with elevated serum TSP-2 levels tended to have pitting scars and/or ulcers. TSP-2 knockdown resulted in the down-regulation of type I collagen expression and the up-regulation of miR-7, one of the miRNAs with an inhibitory effect on collagen expression. Expression levels of miR-7 were also up-regulated in SSc dermal fibroblasts both in vivo and in vitro. Taken together, these findings suggest that the increased extracellular TSP-2 deposition in SSc fibroblasts may contribute to tissue fibrosis by inducing collagen expression. Down-regulation of intracellular TSP-2 synthesis and the subsequent miR-7 up-regulation in SSc fibroblasts may be due to a negative feedback mechanism that prevents increased extracellular TSP-2 deposition and/or tissue fibrosis. Thus, TSP-2 may play an important role in the maintenance of fibrosis and angiopathy in patients with SSc. (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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