Novel Concepts in Systemic Sclerosis Pathogenesis: Role for miRNAs

Szabó, I.; Muntean, Laura; Crişan, Tania O.; Rednic, Voicu; Simu, Claudia; Rednic, Simona

doi:10.3390/biomedicines9101471

Cited by 18 publications

(12 citation statements)

References 103 publications

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“…Systemic sclerosis (SSc) is an autoimmune multi-organ disease characterized by vasculopathy and fibrosis involving the skin and/or lungs, heart and kidneys [ 315 , 316 , 317 ]. Multiple studies described lower vitamin D levels in SSc patients [ 318 , 319 ].…”

Section: Vitamin D and Immune-related And Autoimmune Diseasesmentioning

confidence: 99%

An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases

Simu

Rednic

Grama

et al. 2022

IJMS

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Vitamin D intervenes in calcium and phosphate metabolism and bone homeostasis. Experimental studies have shown that 1,25-dihydroxyvitamin D (calcitriol) generates immunologic activities on the innate and adaptive immune system and endothelial membrane stability. Low levels of serum 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of developing immune-related diseases such as psoriasis, type 1 diabetes, multiple sclerosis, and autoimmune diseases. Various clinical trials describe the efficacy of supplementation of vitamin D and its metabolites for treating these diseases that result in variable outcomes. Different disease outcomes are observed in treatment with vitamin D as high inter-individual difference is present with complex gene expression in human peripheral blood mononuclear cells. However, it is still not fully known what level of serum 25(OH)D is needed. The current recommendation is to increase vitamin D intake and have enough sunlight exposure to have serum 25(OH)D at a level of 30 ng/mL (75 nmol/L) and better at 40–60 ng/mL (100–150 nmol/L) to obtain the optimal health benefits of vitamin D.

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Section: Vitamin D and Immune-related And Autoimmune Diseasesmentioning

confidence: 99%

An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases

Simu

Rednic

Grama

et al. 2022

IJMS

Self Cite

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“…Small non-coding RNA sequences (miRNAs) are associated with vascular, immune response, and ECM homeostasis, and upregulation or downregulation of diverse miRNAs has been observed in blood and tissue from SSc patients [ 149 ]. MiR-29a represses α2AP and TIMP-1 expression and recovers the pro-fibrotic phenotype in SSc dermal fibroblasts [ 56 , 150 ].…”

Section: The Role Of α2ap As a Therapeutic Target For Sscmentioning

confidence: 99%

α2-Antiplasmin as a Potential Therapeutic Target for Systemic Sclerosis

Kanno

Shu

2022

Life

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Systemic sclerosis is a connective tissue disease of unknown origin that is characterized by immune system abnormalities, vascular damage, and extensive fibrosis of the skin and visceral organs. α2-antiplasmin is known to be the main plasmin inhibitor and has various functions such as cell differentiation and cytokine production, as well as the regulation of the maintenance of the immune system, endothelial homeostasis, and extracellular matrix metabolism. The expression of α2-antiplasmin is elevated in dermal fibroblasts from systemic sclerosis patients, and the blockade of α2-antiplasmin suppresses fibrosis progression and vascular dysfunction in systemic sclerosis model mice. α2-antiplasmin may have promise as a potential therapeutic target for systemic sclerosis. This review considers the role of α2-antiplasmin in the progression of systemic sclerosis.

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“…In order to understand the molecular pathways involved in SSc pathogenesis, recent attention has been given to the role of epigenetic factors, and in particular to microRNAs (miRNAs), short RNA sequences 20–23 nucleotides in length that are recognized to have a fundamental importance in the regulation of gene expression at the post-transcriptional level [ 29 , 30 ]. Interestingly, several miRNAs associated with vasculopathy and fibro-proliferative alteration have also been found to be dysregulated in SSc patients compared to controls [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs

et al. 2023

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Tissue fibrosis can affect every type of tissue or organ, often leading to organ malfunction; however, the mechanisms involved in this process are not yet clarified. A role has been hypothesized for Human Cytomegalovirus (HCMV) and Human Herpesvirus 6 (HHV-6) infections as triggers of systemic sclerosis (SSc), a severe autoimmune disease causing progressive tissue fibrosis, since both viruses and antiviral immune responses toward them have been detected in patients. Moreover, HCMV or HHV-6A infection was reported to increase the expression of fibrosis-associated transcriptional factors and miRNAs in human dermal fibroblasts. However, it is unlikely that they have separate effects in the infected host, as both viruses are highly prevalent in the human population. Thus, our study aimed to investigate, by quantitative real-time PCR microarray, the impact of HCMV/HHV-6A coinfection on the expression of pro-fibrotic miRNAs in coinfected cells, compared to the effect of single viruses. The results showed a possible synergistic effect of the two viruses on pro-fibrotic miRNA expression, thus suggesting that HCMV and HHV-6 may enhance each other and cooperate at inducing enhanced miRNA-driven fibrosis. These data may also suggest a possible use of virus-induced miRNAs as novel diagnostic or prognostic biomarkers for SSc and its clinical treatment.

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Novel Concepts in Systemic Sclerosis Pathogenesis: Role for miRNAs

Cited by 18 publications

References 103 publications

An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases

An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases

α2-Antiplasmin as a Potential Therapeutic Target for Systemic Sclerosis

Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs

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