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Systemic Sclerosis pp 1–20Cite as

Fibrosis: Overview

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Abstract

Fibrosis, excessive extracellular matrix deposition, in the skin, lung, and other organs is a hallmark of systemic sclerosis (SSc). Fibroblasts isolated from sclerotic lesions, such as the sclerotic skin or lung, in patients with SSc and cultured in vitro are characterized by increased synthesis of collagen and other extracellular matrix proteins, decreased synthesis and activity of matrix metalloproteinases, and increased synthesis of tissue inhibitor of metalloproteinases, consistent with the disease phenotype. The pathogenesis of SSc is still poorly understood, but increasing evidence suggests that transforming growth factor-β (TGF-β) is a key mediator of tissue fibrosis as a consequence of extracellular matrix accumulation in the pathology of SSc. TGF-β regulates diverse biological activities including cell growth, cell death or apoptosis, cell differentiation, and extracellular matrix synthesis. TGF-β is known to induce the expression of extracellular matrix proteins in mesenchymal cells and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the extracellular matrix. This chapter focuses on the mechanism of fibrosis in SSc.

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  1. Department of Dermatology & Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Hironobu Ihn

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  1. Department of Dermatology, Kanazawa University, Kanazawa, Ishikawa, Japan

    Kazuhiko Takehara

  2. Department of Dermatology, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Manabu Fujimoto

  3. Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Tokyo, Japan

    Masataka Kuwana

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Ihn, H. (2016). Fibrosis: Overview. In: Takehara, K., Fujimoto, M., Kuwana, M. (eds) Systemic Sclerosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55708-1_1

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