Journal of Clinical Medicine

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Special Issue Editors

Dr. Francesco Del Galdo

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Guest Editor

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
Interests: systemic sclerosis; Raynauld’s syndrome

Dr. Christopher W. Wasson

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Guest Editor

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
Interests: systemic sclerosis; Raynauld’s syndrome

Dr. Rebecca L. Ross

E-Mail Website
Guest Editor

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
Interests: systemic sclerosis; Raynauld’s syndrome

Special Issue Information

Dear Colleagues,

Systemic Sclerosis (SSc) is surely one of the most intriguing autoimmune diseases and has for decades been completely orphan of effective treatments, burdened by several negative large trials.

In the past few years, the effectiveness of bone marrow transplants and the approval of the first antifibrotic treatment for interstitial lung disease have revamped the enthusiasm for directly targeting the fibrotic process. In this Special Issue of the Journal of Clinical Medicine we aim to offer reviews and original research articles that highlight both profibrotic and immune pathways that may warrant therapeutic targeting.

Dr. Francesco Del Galdo
Dr. Christopher W. Wasson
Dr. Rebecca L. Ross
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

systemic sclerosis
scleroderma
autoimmunity
fibrosis

Published Papers (2 papers)

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Research

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13 pages, 3042 KiB

Open AccessArticle

SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker

by Ilaria Tinazzi, Panji Mulipa, Chiara Colato, Giuseppina Abignano, Andrea Ballarin, Domenico Biasi, Paul Emery, Rebecca L. Ross and Francesco Del Galdo

J. Clin. Med. 2021, 10(24), 5820; https://doi.org/10.3390/jcm10245820 - 13 Dec 2021

Cited by 9 | Viewed by 2389

Abstract

Secreted Frizzled Receptor Protein 4 (SFRP4) has been shown to be increased in Scleroderma (SSc). To determine its role in immune-driven fibrosis, we analysed SSc and sclerotic Chronic Graft Versus Host Disease (sclGVHD) biosamples; skin biopsies (n = 24) from chronic GVHD patients (8 with and 5 without sclGVHD), 8 from SSc and 3 healthy controls (HC) were analysed by immunofluorescence (IF) and SSc patient sera (n = 77) assessed by ELISA. Epithelial cell lines used for in vitro Epithelial-Mesenchymal-Transition (EMT) assays and analysed by Western Blot, RT-PCR and immunofluorescence. SclGVHD skin biopsies resembled pathologic features of SSc. IF of fibrotic skin biopsies indicated the major source of SFRP4 expression were dermal fibroblasts, melanocytes and vimentin positive/caveolin-1 negative cells in the basal layer of the epidermis. In vitro studies showed increased vimentin and SFRP4 expression accompanied with decreased caveolin-1 expression during TGFβ-induced EMT. Additionally, SFRP4 serum concentration correlated with severity of lung and skin fibrosis in SSc. In conclusion, SFRP4 expression is increased during skin fibrosis in two different immune-driven conditions, and during an in vitro EMT model. Its serum levels correlate with skin and lung fibrosis in SSc and may function as biomarker of EMT. Further studies are warranted to elucidate the role of SFRP4 in EMT within the pathogenesis of tissue fibrosis. Full article

(This article belongs to the Special Issue Systemic Sclerosis—Pathogenesis and Emerging Therapies)

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Review

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14 pages, 888 KiB

Open AccessReview

Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target

by Sonsoles Piera-Velazquez and Sergio A. Jimenez

J. Clin. Med. 2021, 10(20), 4791; https://doi.org/10.3390/jcm10204791 - 19 Oct 2021

Cited by 23 | Viewed by 4725

Abstract

Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise mechanisms mediating oxidative stress development in SSc and its pathogenetic effects have not been fully elucidated. The participation of the NADPH oxidase NOX4, has been suggested and experimentally supported by the demonstration that SSc dermal fibroblasts display constitutively increased NOX4 expression and that reduction or abrogation of NOX4 effects decreased ROS production and the expression of genes encoding fibrotic proteins. Furthermore, NOX4-stimulated ROS production may be involved in the development of certain endothelial and vascular abnormalities and may even participate in the generation of SSc-specific autoantibodies. Collectively, these observations suggest NOX4 as a novel therapeutic target for SSc. Full article

(This article belongs to the Special Issue Systemic Sclerosis—Pathogenesis and Emerging Therapies)

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