期刊
JOURNAL OF DERMATOLOGICAL SCIENCE
卷 70, 期 3, 页码 151-158出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2013.03.005
关键词
Fibrosis; Connective tissue; Signaling; miRNA
类别
A variety of fibrosing connective tissue disorders of the skin have been described. They all share a characteristic activation of fibroblasts. resulting in excessive production and deposition of extracellular matrix whereas their etiologies, incidence rates and clinical appearances differ dramatically in part. As effective treatment options are still not on hand, the understanding of cutaneous fibrogenesis needs to be improved. This review focuses on the molecular differences and similarities of the major fibrosing skin disorders namely systemic sclerosis, localized scleroderma, keloid and hypertrophic scars, Eosinophilic fasciitis, Lichen sclerosus and graft-versus-host-disease. Abnormalities in ECM turnover and the impact of matrix-metalloproteases were closely examined. It could be concluded, that besides increased collagen synthesis, modified ECM degradation is an as important factor in cutaneous fibrogenesis. The influence of immune components such as HLA haplotypes and the production of auto-antibodies is crucial for some of the diseases, but not decisive for skin fibrosis in general. A great number of cytokines was reported to be differentially regulated in the respective disorders among whom the components of the gp130/STAT3 signaling pathway seem to be of pivotal importance. Furthermore, the role of miRNAs in the pathogenesis of fibrosing connective tissue diseases of the skin was analyzed according to the current state of knowledge. In summary, this review gives an explicit overview of the various molecular mechanisms leading to fibrosis in the skin and the underlying connective tissue and reveals the most promising targets for future therapeutic approaches. (c) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
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