Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis

Vreća, Miša; Andjelković, Marina; Tos̆ić, Nataša; Zeković, Ana; Pavlović, Sonja; Spasovski, Vesna

doi:10.1016/j.imlet.2018.10.002

Cited by 12 publications

(14 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The strong signal within the Xq28 region is also related to overexpression of MECP2 gene (related to diffuse cutaneous SSc) in SSc (31). A recent study reported reduced expression levels of IRAK1 messenger RNA (inter-related to MEP2) in peripheral blood mononuclear cells (PBMCs) in SSc patients compared to controls, but also lower in male patients compared to females and appears to be associated with severe skin involvement (32). PBMC expression of miR-146a (which downregulates IRAK1) is also reduced in SSc patients; particularly in males and those with severe skin involvement (32).…”

Section: Pathogenesis (Jp)mentioning

confidence: 99%

“…A recent study reported reduced expression levels of IRAK1 messenger RNA (inter-related to MEP2) in peripheral blood mononuclear cells (PBMCs) in SSc patients compared to controls, but also lower in male patients compared to females and appears to be associated with severe skin involvement (32). PBMC expression of miR-146a (which downregulates IRAK1) is also reduced in SSc patients; particularly in males and those with severe skin involvement (32). Other genes such as IL13RA2 have been shown to be associated with SSc in female populations (33).…”

Section: Pathogenesis (Jp)mentioning

confidence: 99%

See 1 more Smart Citation

Gender-related differences in systemic sclerosis

Hughes

Pauling

Armstrong-James

et al. 2020

Autoimmunity Reviews

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease which is characterised by widespread tissue fibrosis of the skin and internal organs, widespread vasculopathic alterations and immune system abnormalities. The condition is more common in women, but has a more severe expression of disease and higher mortality in men. Although the aetiopathogenesis of SSc is not yet fully understood, there is emerging evidence of important differences between men and women with the disease. This review brings together the current evidence on sex differences in SSc including epidemiology, pathophysiology, clinical expression of disease, mortality, SSc in transgender individuals, and psychosocial aspects of disease.

show abstract

Section: Pathogenesis (Jp)mentioning

confidence: 99%

Section: Pathogenesis (Jp)mentioning

confidence: 99%

Gender-related differences in systemic sclerosis

Hughes

Pauling

Armstrong-James

et al. 2020

Autoimmunity Reviews

View full text Add to dashboard Cite

show abstract

“…Although neither IRAK1 rs3027898 nor miR-146a rs2910164 variants were directly associated with SSc susceptibility, miR-146a rs2910164 genotype and allele distribution correlated with the presence of lung fibrosis. 111 As far as gene expression is concerned, both IRAK1 and miR-146a were found to be downregulated in PBMCs from SSc patients, with a strong negative correlation between IRAK1…”

Section: X-linked Single Nucleotide Polymorphismsmentioning

confidence: 99%

“…Indeed, a significant increase in miR-146a expression in male SSc patients was accompanied by decreased IRAK1 mRNA levels, suggesting a direct regulation of IRAK1 gene expression by this specific miRNA. 111…”

Section: X-linked Genetic and Epigenetic Modifications In Sscmentioning

confidence: 99%

The contribution of epigenetics to the pathogenesis and gender dimorphism of systemic sclerosis: a comprehensive overview

Fioretto

Rosa

Romano

et al. 2020

Therapeutic Advances in Musculoskeletal

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a life-threatening connective tissue disorder of unknown etiology characterized by widespread vascular injury and dysfunction, impaired angiogenesis, immune dysregulation and progressive fibrosis of the skin and internal organs. Over the past few years, a new trend of investigations is increasingly reporting aberrant epigenetic modifications in genes related to the pathogenesis of SSc, suggesting that, besides genetics, epigenetics may play a pivotal role in disease development and clinical manifestations. Like many other autoimmune diseases, SSc presents a striking female predominance, and even if the reason for this gender imbalance has yet to be completely understood, it appears that the X chromosome, which contains many gender and immune-related genes, could play a role in such gender-biased prevalence. Besides a short summary of the genetic background of SSc, in this review we provide a comprehensive overview of the most recent insights into the epigenetic modifications which underlie the pathophysiology of SSc. A particular focus is given to genetic variations in genes located on the X chromosome as well as to the main X-linked epigenetic modifications that can influence SSc susceptibility and clinical phenotype. On the basis of the most recent advances, there is realistic hope that integrating epigenetic data with genomic, transcriptomic, proteomic and metabolomic analyses may provide in the future a better picture of their functional implications in SSc, paving the right way for a better understanding of disease pathogenesis and the development of innovative therapeutic approaches.

show abstract

“…miR-29a was down-regulated in the skin and dermal fibroblasts of SSc patients, compared to controls, and it has been implicated in the regulation of collagen expression and apoptosis [143,144,145]. Polymorphisms, rs2910164C/G, of miR-146a were associated with lung fibrosis development, telangiectasia, and SSc onset [146,147]. Wermuth et al also evaluated the effects of isolated serum exosomes on the gene expression and biosynthetic activity of normal human dermal fibroblasts [140].…”

Section: Exosomes: New Perspective For the Diagnosis And Treatmentmentioning

confidence: 99%

Exosomes in Systemic Sclerosis: Messengers Between Immune, Vascular and Fibrotic Components?

Colletti

Galardi

Santis

et al. 2019

IJMS

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a rare autoimmune disease, characterized by vasculopathy and fibrosis of the skin and internal organs. This disease is still considered incurable and is associated with a high risk of mortality, which is related to fibrotic events. An early diagnosis is useful for preventing complications, and targeted therapies reduce disease progression and ameliorate patients’ quality of life. Nevertheless, there are no validated biomarkers for early diagnosis with predictive prognostic value. Exosomes are membrane vesicles, transporting proteins and nucleic acids that may be delivered to target cells, which influences cellular behavior. They play important roles in cell–cell communication, both in physiological and pathological conditions, and may be useful as circulating biomarkers. Recent evidences suggest a role for these microvesicles in the three main aspects related to the pathogenesis of SSc (immunity, vascular damage, and fibrosis). Moreover, exosomes are of particular interest in the field of nano-delivery and are used as biological carriers. In this review, we report the latest information concerning SSc pathogenesis, clinical aspects of SSc, and current approaches to the treatment of SSc. Furthermore, we indicate a possible role of exosomes in SSc pathogenesis and suggest their potential use as diagnostic and prognostic biomarkers, as well as therapeutic tools.

show abstract

Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis

Cited by 12 publications

References 58 publications

Gender-related differences in systemic sclerosis

Gender-related differences in systemic sclerosis

The contribution of epigenetics to the pathogenesis and gender dimorphism of systemic sclerosis: a comprehensive overview

Exosomes in Systemic Sclerosis: Messengers Between Immune, Vascular and Fibrotic Components?

Contact Info

Product

Resources

About