https://scholars.lib.ntu.edu.tw/handle/123456789/593937
標題: | Pathogenic Roles of Autoantibodies and Aberrant Epigenetic Regulation of Immune and Connective Tissue Cells in the Tissue Fibrosis of Patients with Systemic Sclerosis | 作者: | Tsai, Chang-Youh SONG-CHOU HSIEH Wu, Tsai-Hung KO-JEN LI CHIEH-YU SHEN Liao, Hsien-Tzung CHENG-HAN WU YU-MIN KUO Lu, Cheng-Shiun CHIA-LI YU |
關鍵字: | TGF-β; Wnt/catenin signal pathway; long non-coding RNA; microRNA; myofibroblast trans-differentiation; non-coding RNA; pro-fibrogenic cytokines; systemic sclerosis; tissue fibrosis | 公開日期: | 27-四月-2020 | 出版社: | MDPI | 卷: | 21 | 期: | 9 | 起(迄)頁: | 3069 | 來源出版物: | International journal of molecular sciences | 摘要: | Systemic sclerosis (SSc) is a multi-system autoimmune disease with tissue fibrosis prominent in the skin and lung. In this review, we briefly describe the autoimmune features (mainly autoantibody production and cytokine profiles) and the potential pathogenic contributors including genetic/epigenetic predisposition, and environmental factors. We look in detail at the cellular and molecular bases underlying tissue-fibrosis which include trans-differentiation of fibroblasts (FBs) to myofibroblasts (MFBs). We also state comprehensively the pro-inflammatory and pro-fibrotic cytokines relevant to MFB trans-differentiation, vasculopathy-associated autoantibodies, and fibrosis-regulating microRNAs in SSc. It is conceivable that tissue fibrosis is mainly mediated by an excessive production of TGF-β, the master regulator, from the skewed Th2 cells, macrophages, fibroblasts, myofibroblasts, and keratinocytes. After binding with TGF-β receptors on MFB, the downstream Wnt/β-catenin triggers canonical Smad 2/3 and non-canonical Smad 4 signaling pathways to transcribe collagen genes. Subsequently, excessive collagen fiber synthesis and accumulation as well as tissue fibrosis ensue. In the later part of this review, we discuss limited data relevant to the role of long non-coding RNAs (lncRNAs) in tissue-fibrosis in SSc. It is expected that these lncRNAs may become the useful biomarkers and therapeutic targets for SSc in the future. The prospective investigations in the development of novel epigenetic modifiers are also suggested. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/593937 | ISSN: | 16616596 | DOI: | 10.3390/ijms21093069 | SDG/關鍵字: | caspase 3; caspase 8; collagen type 1; connective tissue growth factor; cyclin D1; gelatinase A; interleukin 13; interleukin 17; transforming growth factor beta; autoantibody; biological marker; cytokine; apoptosis; disease activity; DNA methylation; DNA sequence; epigenetics; gene expression; human; immunological tolerance; oxidative stress; protein expression; psoriasis; Review; risk factor; signal transduction; skin biopsy; skin fibrosis; systemic sclerosis; upregulation; Wnt signaling; animal; connective tissue cell; disease predisposition; fibrosis; gene expression regulation; genetic epigenesis; genetics; immunology; immunomodulation; metabolism; myofibroblast; pathology; systemic sclerosis; Animals; Autoantibodies; Biomarkers; Connective Tissue Cells; Cytokines; Disease Susceptibility; DNA Methylation; Epigenesis, Genetic; Fibrosis; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Humans; Immunomodulation; Myofibroblasts; Risk Factors; Scleroderma, Systemic; Signal Transduction |
顯示於: | 醫學系 |
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