The Epigenetic Regulation of Scleroderma and Its Clinical Application.

The Epigenetic Regulation of Scleroderma and Its Clinical Application. Adv Exp Med Biol. 2020;1253:375-403 Authors: Luo Y, Xiao R Abstract Scleroderma (systemic sclerosis; SSc) is a complex and highly heterogeneous multisystem rheumatic disease characterized by vascular abnormality, immunologic derangement, and excessive deposition of extracellular matrix (ECM) proteins. To date, the etiology of this life-threatening disorder remains not fully clear. More and more studies show epigenetic modifications play a vital role. The aberrant epigenetic status of certain molecules such as Fli-1, BMPRII, NRP1, CD70, CD40L, CD11A, FOXP3, KLF5, DKK1, SFRP1, and so on contributes to the pathogenesis of progressive vasculopathy, autoimmune dysfunction, and tissue fibrosis in SSc. Meanwhile, numerous miRNAs including miR-21, miR-29a, miR-196a, miR-202-3p, miR-150, miR-let-7a, and others are involved in the process. In addition, the abnormal epigenetic biomarker levels of CD11a, Foxp3, HDAC2, miR-30b, miR-142-3p, miR-150, miR-5196 in SSc are closely correlated with disease severity. In this chapter, we not only review new advancements on the epigenetic mechanisms involved in the pathogenesis of SSc and potential epigenetic biomarkers, but also discuss the therapeutic potential of epigenetic targeting therapeutics such as DNA methylation inhibitors, histone acetylase inhibitors, and miRNA replacement. PMID: 32445102 [PubMed - as supplied by publisher]
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research

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CONCLUSIONS: GPOEM may be an interesting therapeutic option in patient with SSc and severe gastroparesis after failure of classical treatment. This procedure could be proposed to patients after multidisciplinary discussion. PMID: 32634328 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
AbstractGenomic predisposition cannot explain the onset of complex diseases, as well illustrated by the largely incomplete concordance among monozygotic twins. Epigenetic mechanisms, including DNA methylation, chromatin remodelling and non-coding RNA, are considered to be the link between environmental stimuli and disease onset on a permissive genetic background in autoimmune and chronic inflammatory diseases. The paradigmatic cases of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren ’s syndrome (SjS) and type-1 diabetes (T1D) share the loss of immunological tolerance t...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review. J Autoimmun. 2020 Jul 01;:102510 Authors: Liu Y, Wang J, Luo S, Zhan Y, Lu Q Abstract Autoimmune diseases are common diseases of the immune system that are characterized by the loss of self-tolerance and the production of autoantibodies; the breakdown of immune tolerance and the prolonged inflammatory reaction are undisputedly core steps in the initiation and maintenance of autoimmunity. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear hormo...
Source: Journal of Autoimmunity - Category: Allergy & Immunology Authors: Tags: J Autoimmun Source Type: research
Fibrosis is the extensive deposition of fibrous connective tissue, and it is characterized by the accumulation of collagen and other extracellular matrix (ECM) components. Fibrosis is essential for wound healing and tissue repair in response to a variety of triggers, which include infection, inflammation, autoimmune disorder, degenerative disease, tumor, and injury. Fibrotic remodeling in various diseases, such as liver cirrhosis, pulmonary fibrosis, renal interstitial fibrosis, myocardial infarction, systemic sclerosis (SSc), and graft-versus-host disease (GVHD), can impair organ function, causing high morbidity and morta...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
A man who was diagnosed with rheumatoid arthritis (RA) five years ago sees his rheumatologist for a follow-up visit. Fortunately, his arthritis is well controlled through medication. He can walk and do all his daily activities without pain. But over the past six months, he’s been feeling short of breath when climbing stairs. He has an annoying dry cough, too. COVID-19? That’s ruled out quickly. But a CT scan of his chest reveals early fibrosis (scarring) of the lungs, most likely related to rheumatoid arthritis. “I can finally walk normally, and now I can’t breathe when I walk!” says the frust...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Arthritis Autoimmune diseases Health Inflammation Lung disease Source Type: blogs
Chronic graft-versus host disease (cGVHD) remains a significant cause of morbidity and mortality for up to 70% of patients receiving allogeneic (allo) hematopoietic cell transplantation (HCT) [1,2]. A syndrome that presents with clinical findings resembling autoimmune and immunological disorders such as scleroderma, wasting syndrome, and bronchiolitis obliterans, cGVHD may affect any body system including the liver, lungs and gastrointestinal system [3]. Risk factors for the development of cGVHD include older age of the donor and the recipient at the time of allo-HCT, human leukocyte antigen mismatch between the donor and ...
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
AbstractPurpose of ReviewSystemic sclerosis (SSc) is an autoimmune connective tissue disease in which there is an activation of fibroblast to a myofibroblast that secretes huge amounts of extracellular matrix. Currently, no treatment exists that modifies the fibrosis elements and new therapeutic targets are badly needed. This review examines the current state of treatments and emerging therapeutics.Recent FindingsNintedanib was found to significantly reduce the rate of decline in SSc associated FVC, although it has no benefit on skin fibrosis. New cannabinoid receptor2 agonist has shown superb effects in phase II and resul...
Source: Current Rheumatology Reports - Category: Rheumatology Source Type: research
Resolvins, the member of specialized pro-resolving mediators, are produced from omega-3 polyunsaturated fatty acids as a response to an acute inflammatory process in that termination and resolution of inflammation. In the acute inflammation, these lipid mediators limit polymorphonuclear cells infiltration, proinflammatory cytokine production; promote efferocytosis, and regulate several cell types being important roles in innate and adaptive immunity. Any dysregulation or defect of the resolution phase result in prolonged, persistent inflammation and eventually fibrosis. Resolvins are implicated in the development of variou...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Autoimmune disease is the leading cause of morbidity among women. For largely unknown reasons, many autoimmune diseases show a striking female bias. Fibrosis is a common feature of female-biased autoimmune diseases. This is exemplified by systemic sclerosis (SSc), a debilitating disease marked by progressive skin hardening and organ damage that affects women at ninefold the rate of men. We previously identified the transcriptional cofactor VGLL3 as an immune regulator enriched in female skin whose targets overlap significantly with genes dysregulated in SSc.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Adaptive and Auto-Immunity Source Type: research
Scleroderma (Systemic sclerosis) is an autoimmune disease that leads to excess production of collagen and other matrix proteins in the skin and other organs. Graft-vs-host disease, a major complication of stem cell transplant, can cause similar scarring of the skin. We hypothesized that scleroderma and the sclerotic form of graft-vs-host disease have overlapping immune-mediated pathogenesis. To examine pathways that drive fibrosis, we performed single-cell RNA sequencing from skin biopsies of patients with diffuse scleroderma and sclerotic graft-vs-host disease compared to normal controls.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Cell-Cell Interactions in the Skin Source Type: research
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