International journal of molecular sciences, 2020-04, Vol.21 (9), p.3069
2020
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- Autor(en) / Beteiligte
- Titel
- Pathogenic Roles of Autoantibodies and Aberrant Epigenetic Regulation of Immune and Connective Tissue Cells in the Tissue Fibrosis of Patients with Systemic Sclerosis
- Ist Teil von
- International journal of molecular sciences, 2020-04, Vol.21 (9), p.3069
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms21093069Titel-ID: cdi_doaj_primary_oai_doaj_org_article_f1a348035d774323a9b72a143be7c575
- Format
- –
- Schlagworte
- Animals, Autoantibodies, Autoantibodies - immunology, Autoimmune diseases, Biomarkers, Collagen, Connective Tissue Cells - immunology, Connective Tissue Cells - metabolism, Cytokines, Cytokines - metabolism, Deoxyribonucleic acid, Differentiation, Disease Susceptibility, DNA, DNA Methylation, Enzymes, Epigenesis, Genetic, Epigenetics, Fibrosis, Gene expression, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Gene loci, Helper cells, Humans, Hyperactivity, Immunomodulation - genetics, Inflammation, Ischemia, Keratinocytes, long non-coding RNA, Lymphocytes, Lymphocytes T, Macrophages, microRNA, miRNA, myofibroblast trans-differentiation, Myofibroblasts - metabolism, Non-coding RNA, Proteins, Review, Risk Factors, RNA polymerase, Scleroderma, Scleroderma, Systemic - etiology, Scleroderma, Systemic - metabolism, Scleroderma, Systemic - pathology, Signal Transduction, Skin, Smad protein, Systemic sclerosis, Therapeutic applications, tissue fibrosis, Vascular diseases, Wnt protein, Wnt/catenin signal pathway, β-Catenin