Biomedicines

Editorial

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Open AccessEditorial

Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis

by Michal Tomcik

Biomedicines 2022, 10(12), 3053; https://doi.org/10.3390/biomedicines10123053 - 28 Nov 2022

Viewed by 1041

Abstract

Systemic sclerosis (scleroderma, SSc) is one of the most challenging rheumatic diseases, characterized by vasculopathy, dysregulation of the immune response, and progressive tissue fibrosis affecting the skin, lungs, heart, digestive tract, and kidneys [...] Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

Research

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12 pages, 504 KiB

Open AccessArticle

Delphi-Based Consensus on Interstitial Lung Disease Screening in Patients with Connective Tissue Diseases (Croatian National-Based Study)

by Mislav Radić, Srđan Novak, Marko Barešić, Ana Hećimović, Dijana Perković, Jasna Tekavec-Trkanjec, Miroslav Mayer, Višnja Prus, Jadranka Morović-Vergles, Daniela Marasović Krstulović, Mislav Cerovec, Ljiljana Bulat Kardum, Miroslav Samaržija and Branimir Anić

Biomedicines 2022, 10(12), 3291; https://doi.org/10.3390/biomedicines10123291 - 19 Dec 2022

Cited by 5 | Viewed by 2354

Abstract

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of [...] Read more.

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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12 pages, 825 KiB

Open AccessArticle

Clinical Predictors of Lung-Function Decline in Systemic-Sclerosis-Associated Interstitial Lung Disease Patients with Normal Spirometry

by Tamas Nagy, Nora Melinda Toth, Erik Palmer, Lorinc Polivka, Balazs Csoma, Alexandra Nagy, Noémi Eszes, Krisztina Vincze, Enikő Bárczi, Anikó Bohács, Ádám Domonkos Tárnoki, Dávid László Tárnoki, György Nagy, Emese Kiss, Pál Maurovich-Horvát and Veronika Müller

Biomedicines 2022, 10(9), 2129; https://doi.org/10.3390/biomedicines10092129 - 31 Aug 2022

Cited by 6 | Viewed by 1983

Abstract

Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients [...] Read more.

Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Progressive pulmonary fibrosis (PPF) is defined as progression in 2 domains including clinical, radiological or lung-function parameters. Our aim was to assess predictors of functional decline in SSc-ILD patients and compare disease behavior to that in idiopathic pulmonary fibrosis (IPF) patients. Patients with normal forced vital capacity (FVC > 80% predicted; SSc-ILD: n = 31; IPF: n = 53) were followed for at least 1 year. Predictors of functional decline including clinical symptoms, comorbidities, lung-function values, high-resolution CT pattern, and treatment data were analyzed. SSc-ILD patents were significantly younger (59.8 ± 13.1) and more often women (93 %) than IPF patients. The median yearly FVC decline was similar in both groups (SSc-ILD = −67.5 and IPF = −65.3 mL/year). A total of 11 SSc-ILD patients met the PPF criteria for functional deterioration, presenting an FVC decline of −153.9 mL/year. Cough and pulmonary hypertension were significant prognostic factors for SSc-ILD functional progression. SSc-ILD patients with normal initial spirometry presenting with cough and PH are at higher risk for showing progressive functional decline. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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18 pages, 865 KiB

Open AccessArticle

MiRNAs in Systemic Sclerosis Patients with Pulmonary Arterial Hypertension: Markers and Effectors

by Mor Zaaroor Levy, Noa Rabinowicz, Maia Yamila Kohon, Avshalom Shalom, Ariel Berl, Tzipi Hornik-Lurie, Liat Drucker, Shelly Tartakover Matalon and Yair Levy

Biomedicines 2022, 10(3), 629; https://doi.org/10.3390/biomedicines10030629 - 08 Mar 2022

Cited by 4 | Viewed by 2353

Abstract

Background: Pulmonary arterial hypertension (PAH) is a major cause of death in systemic sclerosis (SSc). Early detection may improve patient outcomes. Methods: We searched for circulating miRNAs that would constitute biomarkers in SSc patients with PAH (SSc-PAH). We compared miRNA levels and laboratory [...] Read more.

Background: Pulmonary arterial hypertension (PAH) is a major cause of death in systemic sclerosis (SSc). Early detection may improve patient outcomes. Methods: We searched for circulating miRNAs that would constitute biomarkers in SSc patients with PAH (SSc-PAH). We compared miRNA levels and laboratory parameters while evaluating miRNA levels in white blood cells (WBCs) and myofibroblasts. Results: Our study found: 1) miR-26 and miR-let-7d levels were significantly lower in SSc-PAH (n = 12) versus SSc without PAH (SSc-noPAH) patients (n = 25); 2) a positive correlation between miR-26 and miR-let-7d and complement-C3; 3) GO-annotations of genes that are miR-26/miR-let-7d targets and that are expressed in myofibroblast cells, suggesting that these miRNAs regulate the TGF-β-pathway; 4) reduced levels of both miRNAs accompanied fibroblast differentiation to myofibroblasts, while macitentan (endothelin receptor-antagonist) increased the levels. WBCs of SSc-noPAH and SSc-PAH patients contained equal amounts of miR-26/miR-let-7d. During the study, an echocardiograph that predicted PAH development, showed increased pulmonary artery pressure in three SSc-noPAH patients. At study initiation, those patients and an additional SSc-noPAH patient, who eventually developed PAH, had miR-let-7d/miR-26 levels similar to those of SSc-PAH patients. This implies that reduced miR-let-7d/miR-26 levels might be an early indication of PAH. Conclusions: miR-26 and miR-let-7d may be serological markers for SSc-PAH. The results of our study suggest their involvement in myofibroblast differentiation and complement pathway activation, both of which are active in PAH development. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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15 pages, 2778 KiB

Open AccessArticle

Plasma Metabolomic Profiling Reveals Four Possibly Disrupted Mechanisms in Systemic Sclerosis

by Thomas Bögl, Franz Mlynek, Markus Himmelsbach, Norbert Sepp, Wolfgang Buchberger and Marija Geroldinger-Simić

Biomedicines 2022, 10(3), 607; https://doi.org/10.3390/biomedicines10030607 - 04 Mar 2022

Cited by 9 | Viewed by 2621

Abstract

Systemic sclerosis (SSc) is a rare systemic autoimmune disorder marked by high morbidity and increased risk of mortality. Our study aimed to analyze metabolomic profiles of plasma from SSc patients by using targeted and untargeted metabolomics approaches. Furthermore, we aimed to detect biochemical [...] Read more.

Systemic sclerosis (SSc) is a rare systemic autoimmune disorder marked by high morbidity and increased risk of mortality. Our study aimed to analyze metabolomic profiles of plasma from SSc patients by using targeted and untargeted metabolomics approaches. Furthermore, we aimed to detect biochemical mechanisms relevant to the pathophysiology of SSc. Experiments were performed using high-performance liquid chromatography coupled to mass spectrometry technology. The investigation of plasma samples from SSc patients (n = 52) compared to a control group (n = 48) allowed us to identify four different dysfunctional metabolic mechanisms, which can be assigned to the kynurenine pathway, the urea cycle, lipid metabolism, and the gut microbiome. These significantly altered metabolic pathways are associated with inflammation, vascular damage, fibrosis, and gut dysbiosis and might be relevant for the pathophysiology of SSc. Further studies are needed to explore the role of these metabolomic networks as possible therapeutic targets of SSc. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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13 pages, 1269 KiB

Open AccessArticle

Treatment and Systemic Sclerosis Interstitial Lung Disease Outcome: The Overweight Paradox

by Alexandra Nagy, Erik Palmer, Lorinc Polivka, Noemi Eszes, Krisztina Vincze, Eniko Barczi, Aniko Bohacs, Adam Domonkos Tarnoki, David Laszlo Tarnoki, György Nagy, Emese Kiss, Pal Maurovich-Horvat and Veronika Müller

Biomedicines 2022, 10(2), 434; https://doi.org/10.3390/biomedicines10020434 - 13 Feb 2022

Cited by 5 | Viewed by 2410

Abstract

(1) Background: Systemic sclerosis (SSc) is frequently associated with interstitial lung diseases (ILDs). The progressive form of SSc-ILD often limits patient survival. The aim of our study is to evaluate the clinical characteristics and predictors of lung function changes in SSc-ILD patients treated [...] Read more.

(1) Background: Systemic sclerosis (SSc) is frequently associated with interstitial lung diseases (ILDs). The progressive form of SSc-ILD often limits patient survival. The aim of our study is to evaluate the clinical characteristics and predictors of lung function changes in SSc-ILD patients treated in a real-world setting. (2) Methods: All SSc-ILD cases previously confirmed by rheumatologists and a multidisciplinary ILD team between January 2017 and June 2019 were included (n = 54). The detailed medical history, clinical parameters and HRCT were analyzed. The longitudinal follow-up for pulmonary symptoms, functional parameters and treatment were performed for at least 2 years in no treatment, immunosuppression and biological treatment subgroups. (3) Results: In SSc-ILD patients (age 58.7 ± 13.3 years, 87.0% women), the main symptoms included dyspnea, cough, crackles and the Raynaud’s phenomenon. The functional decline was most prominent in untreated patients, and a normal body mass index (BMI < 25 kg/m²) was associated with a significant risk of deterioration. The majority of patients improved or were stable during follow-up. The progressive fibrosing-ILD criteria were met by 15 patients, the highest proportion being in the untreated subgroup. (4) Conclusions: SSc-ILD patients who are overweight are at a lower risk of the functional decline and progressive phenotype especially affecting untreated patients. The close monitoring of lung involvement and a regular BMI measurement are advised and early treatment interventions are encouraged. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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7 pages, 17233 KiB

Open AccessArticle

Bisphosphonates for the Treatment of Calcinosis Cutis—A Retrospective Single-Center Study

by Lilian Rauch, Rüdiger Hein, Tilo Biedermann, Kilian Eyerich and Felix Lauffer

Biomedicines 2021, 9(11), 1698; https://doi.org/10.3390/biomedicines9111698 - 16 Nov 2021

Cited by 12 | Viewed by 2274

Abstract

(1) Background: Calcinosis cutis is a frequent symptom of autoimmune connective tissue diseases leading to pain, transcutaneous expulsion of calcified material and bacterial superinfection. There is a high need for new therapeutic options as no standardized treatment algorithm is established. While case reports [...] Read more.

(1) Background: Calcinosis cutis is a frequent symptom of autoimmune connective tissue diseases leading to pain, transcutaneous expulsion of calcified material and bacterial superinfection. There is a high need for new therapeutic options as no standardized treatment algorithm is established. While case reports indicate beneficial effects of bisphosphonates, standardized evaluation of treatment effects is missing. (2) Methods: In this retrospective analysis we evaluate the effects of intravenous pamidronate, a second-generation bisphosphonate, in seven patients with calcinosis cutis using consecutive clinical pictures, radiological examinations and patient’s subjective evaluation. (3) Results: 5/6 patients reported a reduction of pain, improvement of general condition and cessation of calcinosis progression. Regression of skin lesions was detectable in clinical pictures of 2/6 patients, while 1/6 patients had stable disease. Radiological examination revealed improvement or stable disease in 3/5 patients. Fever was the most common side effect. One out of seven patients developed osteonecrosis of the jaw. (4) Conclusions: Bisphosphonates appear to have beneficial effects in a subgroup of calcinosis cutis patients. While patient’s subjective evaluation was mainly positive, objective assessments showed improvement in approximately half of the cases. With regard to potential severe side effects, a careful risk-benefit evaluation is necessary before treatment initiation. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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18 pages, 3630 KiB

Open AccessArticle

Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin

by Hana Štorkánová, Lenka Štorkánová, Adéla Navrátilová, Viktor Bečvář, Hana Hulejová, Sabína Oreská, Barbora Heřmánková, Maja Špiritović, Radim Bečvář, Karel Pavelka, Jiří Vencovský, Jörg H. W. Distler, Ladislav Šenolt and Michal Tomčík

Biomedicines 2021, 9(6), 650; https://doi.org/10.3390/biomedicines9060650 - 07 Jun 2021

Cited by 5 | Viewed by 2520 | Correction

Abstract

Our previous study demonstrated that heat shock protein 90 (Hsp90) is overexpressed in the involved skin of patients with systemic sclerosis (SSc) and in experimental dermal fibrosis. Pharmacological inhibition of Hsp90 prevented the stimulatory effects of transforming growth factor-beta on collagen synthesis and [...] Read more.

Our previous study demonstrated that heat shock protein 90 (Hsp90) is overexpressed in the involved skin of patients with systemic sclerosis (SSc) and in experimental dermal fibrosis. Pharmacological inhibition of Hsp90 prevented the stimulatory effects of transforming growth factor-beta on collagen synthesis and the development of dermal fibrosis in three preclinical models of SSc. In the next step of the preclinical analysis, herein, we aimed to evaluate the efficacy of an Hsp90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), in the treatment of established experimental dermal fibrosis induced by bleomycin. Treatment with 17-DMAG demonstrated potent antifibrotic and anti-inflammatory properties: it decreased dermal thickening, collagen content, myofibroblast count, expression of transforming growth factor beta receptors, and pSmad3-positive cell counts, as well as leukocyte infiltration and systemic levels of crucial cytokines/chemokines involved in the pathogenesis of SSc, compared to vehicle-treated mice. 17-DMAG effectively prevented further progression and may induce regression of established bleomycin-induced dermal fibrosis to an extent comparable to nintedanib. These findings provide further evidence of the vital role of Hsp90 in the pathophysiology of SSc and characterize it as a potential target for the treatment of fibrosis with translational implications due to the availability of several Hsp90 inhibitors in clinical trials for other indications. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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Review

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29 pages, 2120 KiB

Open AccessReview

Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis

by Hanna Graßhoff, Konstantinos Fourlakis, Sara Comdühr and Gabriela Riemekasten

Biomedicines 2022, 10(9), 2150; https://doi.org/10.3390/biomedicines10092150 - 01 Sep 2022

Cited by 8 | Viewed by 2635

Abstract

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive [...] Read more.

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive B cells and autoantibodies promote and maintain pathologic mechanisms. In addition, autoantibodies in SSc are important biomarkers for predicting clinical phenotype and disease progression. Autoreactive B cells and autoantibodies represent potentially promising targets for therapeutic approaches including B-cell-targeting therapies, as well as strategies for unselective and selective removal of autoantibodies. In this review, we present mechanisms of the innate immune system leading to the generation of autoantibodies, alterations of the B-cell compartment in SSc, autoantibodies as biomarkers and autoantibody-mediated pathologies in SSc as well as potential therapeutic approaches to target these. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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17 pages, 742 KiB

Open AccessReview

Emerging Evidence and Treatment Perspectives from Randomized Clinical Trials in Systemic Sclerosis: Focus on Interstitial Lung Disease

by Caterina Oriana Aragona, Antonio Giovanni Versace, Carmelo Ioppolo, Daniela La Rosa, Rita Lauro, Maria Concetta Tringali, Simona Tomeo, Guido Ferlazzo, William Neal Roberts, Alessandra Bitto, Natasha Irrera and Gianluca Bagnato

Biomedicines 2022, 10(2), 504; https://doi.org/10.3390/biomedicines10020504 - 21 Feb 2022

Cited by 2 | Viewed by 3175

Abstract

Systemic sclerosis (SSc) is a complex rare autoimmune disease with heterogeneous clinical manifestations. Currently, interstitial lung disease (ILD) and cardiac involvement (including pulmonary arterial hypertension) are recognized as the leading causes of SSc-associated mortality. New molecular targets have been discovered and phase II [...] Read more.

Systemic sclerosis (SSc) is a complex rare autoimmune disease with heterogeneous clinical manifestations. Currently, interstitial lung disease (ILD) and cardiac involvement (including pulmonary arterial hypertension) are recognized as the leading causes of SSc-associated mortality. New molecular targets have been discovered and phase II and phase III clinical trials published in the last 5 years on SSc-ILD will be discussed in this review. Details on the study design; the drug tested and its dose; the inclusion and exclusion criteria of the study; the concomitant immunosuppression; the outcomes and the duration of the study were reviewed. The two most common drugs used for the treatment of SSc-ILD are cyclophosphamide and mycophenolate mofetil, both supported by randomized controlled trials. Additional drugs, such as nintedanib and tocilizumab, have been approved to slow pulmonary function decline in SSc-ILD. In this review, we discuss the therapeutic alternatives for SSc management, offering the option to customize the design of future studies to stratify SSc patients and provide a patient-specific treatment according to the new emerging pathogenic features of SSc-ILD. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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18 pages, 1272 KiB

Open AccessReview

Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?

by Anca Cardoneanu, Alexandra Maria Burlui, Luana Andreea Macovei, Ioana Bratoiu, Patricia Richter and Elena Rezus

Biomedicines 2022, 10(2), 318; https://doi.org/10.3390/biomedicines10020318 - 29 Jan 2022

Cited by 14 | Viewed by 3532

Abstract

Systemic sclerosis (SS) is a chronic autoimmune disorder, which has both cutaneous and systemic clinical manifestations. The disease pathogenesis includes a triad of manifestations, such as vasculopathy, autoimmunity, and fibrosis. Interleukin-6 (IL-6) has a special role in SS development, both in vascular damage [...] Read more.

Systemic sclerosis (SS) is a chronic autoimmune disorder, which has both cutaneous and systemic clinical manifestations. The disease pathogenesis includes a triad of manifestations, such as vasculopathy, autoimmunity, and fibrosis. Interleukin-6 (IL-6) has a special role in SS development, both in vascular damage and in the development of fibrosis. In the early stages, IL-6 participates in vascular endothelial activation and apoptosis, leading to the release of damage-associated molecular patterns (DAMPs), which maintain inflammation and autoimmunity. Moreover, IL-6 plays an important role in the development of fibrotic changes by mediating the transformation of fibroblasts into myofibroblasts. All of these are associated with disabling clinical manifestations, such as skin thickening, pulmonary fibrosis, pulmonary arterial hypertension (PAH), heart failure, and dysphagia. Tocilizumab is a humanized monoclonal antibody that inhibits IL-6 by binding to the specific receptor, thus preventing its proinflammatory and fibrotic actions. Anti-IL-6 therapy with Tocilizumab is a new hope for SS patients, with data from clinical trials supporting the favorable effect, especially on skin and lung damage. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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32 pages, 2241 KiB

Open AccessReview

Therapeutic Options for Systemic Sclerosis: Current and Future Perspectives in Tackling Immune-Mediated Fibrosis

by Theodoros-Ioannis Papadimitriou, Arjan van Caam, Peter M. van der Kraan and Rogier M. Thurlings

Biomedicines 2022, 10(2), 316; https://doi.org/10.3390/biomedicines10020316 - 29 Jan 2022

Cited by 10 | Viewed by 5138

Abstract

Systemic sclerosis (SSc) is a severe auto-immune, rheumatic disease, characterized by excessive fibrosis of the skin and visceral organs. SSc is accompanied by high morbidity and mortality rates, and unfortunately, few disease-modifying therapies are currently available. Inflammation, vasculopathy, and fibrosis are the key [...] Read more.

Systemic sclerosis (SSc) is a severe auto-immune, rheumatic disease, characterized by excessive fibrosis of the skin and visceral organs. SSc is accompanied by high morbidity and mortality rates, and unfortunately, few disease-modifying therapies are currently available. Inflammation, vasculopathy, and fibrosis are the key hallmarks of SSc pathology. In this narrative review, we examine the relationship between inflammation and fibrosis and provide an overview of the efficacy of current and novel treatment options in diminishing SSc-related fibrosis based on selected clinical trials. To do this, we first discuss inflammatory pathways of both the innate and acquired immune systems that are associated with SSc pathophysiology. Secondly, we review evidence supporting the use of first-line therapies in SSc patients. In addition, T cell-, B cell-, and cytokine-specific treatments that have been utilized in SSc are explored. Finally, the potential effectiveness of tyrosine kinase inhibitors and other novel therapeutic approaches in reducing fibrosis is highlighted. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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18 pages, 1074 KiB

Open AccessReview

Novel Concepts in Systemic Sclerosis Pathogenesis: Role for miRNAs

by Iulia Szabo, Laura Muntean, Tania Crisan, Voicu Rednic, Claudia Sirbe and Simona Rednic

Biomedicines 2021, 9(10), 1471; https://doi.org/10.3390/biomedicines9101471 - 14 Oct 2021

Cited by 11 | Viewed by 2011

Abstract

Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their [...] Read more.

Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their differential response to external stimuli could explain the protean clinical manifestations of SSc while offering the opportunity of targeted drug development. Small, non-coding RNA sequences (miRNAs) have demonstrated complex interactions between vasculature, immune activation, and extracellular matrices. Distinct miRNA profiles were identified in SSc skin specimens and blood samples containing a wide variety of dysregulated miRNAs. Their target genes are mainly involved in profibrotic pathways, but new lines of evidence also confirm their participation in impaired angiogenesis and aberrant immune responses. Research approaches focusing on earlier stages of the disease and on differential miRNA expression in various tissues could bring novel insights into SSc pathogenesis and validate the clinical utility of miRNAs as biomarkers and therapeutic targets. Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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2 pages, 940 KiB

Open AccessCorrection

Correction: Štorkánová et al. Inhibition of Hsp90 Counteracts the Established Experimental Dermal Fibrosis Induced by Bleomycin. Biomedicines 2021, 9, 650

by Hana Štorkánová, Lenka Štorkánová, Adéla Navrátilová, Viktor Bečvář, Hana Hulejová, Sabína Oreská, Barbora Heřmánková, Maja Špiritović, Radim Bečvář, Karel Pavelka, Jiří Vencovský, Jörg H. W. Distler, Ladislav Šenolt and Michal Tomčík

Biomedicines 2023, 11(10), 2736; https://doi.org/10.3390/biomedicines11102736 - 09 Oct 2023

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In the original publication [...] Full article

(This article belongs to the Special Issue Frontiers of Targeted Therapy and Predictors of Treatment Response in Systemic Sclerosis)

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