scholarly journals Pathogenic Roles of Autoantibodies and Aberrant Epigenetic Regulation of Immune and Connective Tissue Cells in the Tissue Fibrosis of Patients with Systemic Sclerosis

2020 ◽  
Vol 21 (9) ◽  
pp. 3069
Author(s):  
Chang-Youh Tsai ◽  
Song-Chou Hsieh ◽  
Tsai-Hung Wu ◽  
Ko-Jen Li ◽  
Chieh-Yu Shen ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Th2 Cells ◽  
Limited Data ◽  
Autoantibody Production ◽  
Tissue Fibrosis ◽  
Epigenetic Modifiers ◽  
Non Coding Rnas ◽  
Collagen Genes ◽  
Molecular Bases

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.

scholarly journals Contribution of Interleukin-6 to the Pathogenesis of Systemic Sclerosis

2017 ◽  
Vol 2 (2_suppl) ◽  
pp. S6-S12 ◽  
Author(s):  
Yasushi Kawaguchi
Keyword(s):  
Clinical Trials ◽  
Growth Factors ◽  
Systemic Sclerosis ◽  
Interleukin 6 ◽  
Systemic Circulation ◽  
Unknown Etiology ◽  
Tissue Fibrosis ◽  
Biological Features ◽  
The Past

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology, manifesting in patients as tissue fibrosis, endothelial dysfunction, and inflammation. The disease is characterized by autoantibodies, a hallmark of autoimmunity. Various cytokines and growth factors are elevated in the systemic circulation and fibrotic lesions of patients with SSc. In particular, several studies over the past 2 decades have shown that interleukin-6 (IL-6) appears to be involved in the pathogenesis of SSc. Based on the association between aberrant IL-6 production and tissue fibrosis in patients with SSc, the anti-IL-6 receptor antibody, tocilizumab, is being investigated in clinical trials. This article reviews the biological features of IL-6 and the IL-6 receptor; the role of IL-6 in the pathogenesis of SSc; and the potential for IL-6 inhibition to be used in the treatment of patients with SSc.

Epigenetics of scleroderma: Integrating genetic, ethnic, age, and environmental effects

2019 ◽  
Vol 4 (3) ◽  
pp. 238-250 ◽  
Author(s):  
Paula S Ramos
Keyword(s):  
Systemic Sclerosis ◽  
Epigenetic Regulation ◽  
Environmental Effects ◽  
Genetic Factors ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Epigenome Editing ◽  
Non Coding Rnas ◽  
Epigenetic Editing

Scleroderma or systemic sclerosis is thought to result from the interplay between environmental or non-genetic factors in a genetically susceptible individual. Epigenetic modifications are influenced by genetic variation and environmental exposures, and change with chronological age and between populations. Despite progress in identifying genetic, epigenetic, and environmental risk factors, the underlying mechanism of systemic sclerosis remains unclear. Since epigenetics provides the regulatory mechanism linking genetic and non-genetic factors to gene expression, understanding the role of epigenetic regulation in systemic sclerosis will elucidate how these factors interact to cause systemic sclerosis. Among the cell types under tight epigenetic control and susceptible to epigenetic dysregulation, immune cells are critically involved in early pathogenic events in the progression of fibrosis and systemic sclerosis. This review starts by summarizing the changes in DNA methylation, histone modification, and non-coding RNAs associated with systemic sclerosis. It then discusses the role of genetic, ethnic, age, and environmental effects on epigenetic regulation, with a focus on immune system dysregulation. Given the potential of epigenome editing technologies for cell reprogramming and as a therapeutic approach for durable gene regulation, this review concludes with a prospect on epigenetic editing. Although epigenomics in systemic sclerosis is in its infancy, future studies will help elucidate the regulatory mechanisms underpinning systemic sclerosis and inform the design of targeted epigenetic therapies to control its dysregulation.

Role of microRNA in the pathogenesis of systemic sclerosis tissue fibrosis and vasculopathy

2019 ◽  
Vol 18 (11) ◽  
pp. 102396 ◽  
Author(s):  
Tyler W. Henry ◽  
Fabian A. Mendoza ◽  
Sergio A. Jimenez
Keyword(s):  
Systemic Sclerosis ◽  
Tissue Fibrosis

scholarly journals Role of Growth Factors in the Pathogenesis of Tissue Fibrosis in Systemic Sclerosis

2010 ◽  
Vol 6 (4) ◽  
pp. 283-294 ◽  
Author(s):  
Sergio A. Jimenez ◽  
Susan V. Castro ◽  
Sonsoles Piera-Velazquez
Keyword(s):  
Growth Factors ◽  
Systemic Sclerosis ◽  
Tissue Fibrosis

scholarly journals An immunotherapeutic approach to decipher the role of long non-coding RNAs in cancer progression, resistance and epigenetic regulation of immune cells

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Krishnapriya M. Varier ◽  
Hemavathi Dhandapani ◽  
Wuling Liu ◽  
Jialei Song ◽  
Chunlin Wang ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Immune Surveillance ◽  
Specific Gene ◽  
Epigenetic Modifiers ◽  
Cancer Types ◽  
Suppression Of Immune Response ◽  
Non Coding Rnas

AbstractImmunotherapeutic treatments are gaining attention due to their effective anti-tumor response. Particularly, the revolution of immune checkpoint inhibitors (ICIs) produces promising outcomes for various cancer types. However, the usage of immunotherapy is limited due to its low response rate, suggesting that tumor cells escape the immune surveillance. Rapid advances in transcriptomic profiling have led to recognize immune-related long non-coding RNAs (LncRNAs), as regulators of immune cell-specific gene expression that mediates immune stimulatory as well as suppression of immune response, indicating LncRNAs as targets to improve the efficacy of immunotherapy against tumours. Moreover, the immune-related LncRNAs acting as epigenetic modifiers are also under deep investigation. Thus, herein, is a summarised knowledge of LncRNAs and their regulation in the adaptive and innate immune system, considering their importance in autophagy and predicting putative immunotherapeutic responses.

Von Willebrand disease and Weibel-Palade bodies

2010 ◽  
Vol 30 (03) ◽  
pp. 150-155 ◽  
Author(s):  
J. W. Wang ◽  
J. Eikenboom
Keyword(s):  
Platelet Adhesion ◽  
Coagulation Factor ◽  
Von Willebrand Disease ◽  
Inflammatory Factors ◽  
Limited Data ◽  
Storage Organelle ◽  
And Function ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryVon Willebrand factor (VWF) is a pivotal haemostatic protein mediating platelet adhesion to injured endothelium and carrying coagulation factor VIII (FVIII) in the circulation to protect it from premature clearance. Apart from the roles in haemostasis, VWF drives the formation of the endothelial cell specific Weibel-Palade bodies (WPBs), which serve as a regulated storage of VWF and other thrombotic and inflammatory factors. Defects in VWF could lead to the bleeding disorder von Willebrand disease (VWD).Extensive studies have shown that several mutations identified in VWD patients cause an intracellular retention of VWF. However, the effects of such mutations on the formation and function of its storage organelle are largely unknown. This review gives an overview on the role of VWF in WPB biogenesis and summarizes the limited data on the WPBs formed by VWD-causing mutant VWF.

The Role of microRNAs in the Viral Infections

2019 ◽  
Vol 24 (39) ◽  
pp. 4659-4667 ◽  
Author(s):  
Mona Fani ◽  
Milad Zandi ◽  
Majid Rezayi ◽  
Nastaran Khodadad ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Rna Viruses ◽  
Regulation Of Gene Expression ◽  
Molecular Structures ◽  
Main Function ◽  
Cellular Functions ◽  
Viral Genes ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

Systematic Review of the Role of Microparticles in Systemic Sclerosis

2014 ◽  
Vol 9 (4) ◽  
pp. 279-300 ◽  
Author(s):  
James Dunne ◽  
Julius Bankole ◽  
Kevin Keen
Keyword(s):  
Systematic Review ◽  
Systemic Sclerosis

MicroRNAs as Biomarker for Breast Cancer

2020 ◽  
Vol 20 (10) ◽  
pp. 1597-1610 ◽  
Author(s):  
Taru Aggarwal ◽  
Ridhima Wadhwa ◽  
Riya Gupta ◽  
Keshav Raj Paudel ◽  
Trudi Collet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Association Studies ◽  
Large Family ◽  
Breast Cancer Diagnosis ◽  
Cell Multiplication ◽  
Cell Physiology ◽  
Gene Transcript ◽  
Genome Wide Association Studies ◽  
Non Coding Rnas

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.

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