MicroRNAs Implicated in the Immunopathogenesis of Lupus Nephritis

Chafin, Cristen B.; Reilly, Christopher M.

doi:10.1155/2013/430239

Cited by 32 publications

(21 citation statements)

References 112 publications

(137 reference statements)

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“…These mechanisms may affect DNaseI production through gene silencing independently or even in combination. In line with such hypothesis, different miRNA profiles were found in kidney of lupusprone mice with glomerulonephritis as well as in biopsies of lupus patients [35,67,68].…”

Section: Can Epigenetic Mechanisms Explain the Onset Of Tissue Damage?supporting

confidence: 58%

Epigenetics and Systemic Lupus Erythematosus: Unmet Needs

Meroni

Penatti

2015

Clinic Rev Allerg Immunol

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Systemic lupus erythematosus (SLE) is a chronic relapsing-remitting autoimmune disease affecting several organs. Although the management of lupus patients has improved in the last years, several aspects still remain challenging. More sensitive and specific biomarkers for an early diagnosis as well as for monitoring disease activity and tissue damage are needed. Genome-wide association and gene mapping studies have supported the genetic background for SLE susceptibility. However, the relatively modest risk association and the studies in twins have suggested a role for environmental and epigenetic factors, as well as genetic-epigenetic interaction. Accordingly, there is evidence that differences in DNA methylation, histone modifications, and miRNA profiling can be found in lupus patients versus normal subjects. Moreover, impaired DNA methylation on the inactive X-chromosome was suggested to explain, at least in part, the female prevalence of the disease. Epigenetic markers may be help in fulfilling the unmet needs for SLE by offering new diagnostic tools, new biomarkers for monitoring disease activity, or to better characterize patients with a silent clinical disease but with an active serology. Anti-DNA, anti-phospholipid, and anti-Ro/SSA autoantibodies are thought to be pathogenic for glomerulonephritis, recurrent thrombosis and miscarriages, and neonatal lupus, respectively. However, tissue damage occurs occasionally or, in some patients, only in spite of the persistent presence of the antibodies. Preliminary studies suggest that epigenetic mechanisms may explain why the damage takes place in some patients only or at a given time.

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Section: Can Epigenetic Mechanisms Explain the Onset Of Tissue Damage?supporting

confidence: 58%

Epigenetics and Systemic Lupus Erythematosus: Unmet Needs

Meroni

Penatti

2015

Clinic Rev Allerg Immunol

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“…miRNAs play a key role in the activation of innate immunity and the regulation of adaptive immune responses29. In this study, we intended to examine whether immunosuppressant or ASC treatment can modify disease-associated miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE

Choi

Lee

Song

et al. 2016

Sci Rep

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C3.MRL-Faslpr/J mice spontaneously develop high titers of anti-dsDNA, mild glomerular nephritis, and severe lymphoproliferation symptoms. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), and cyclophosphamide treatment in C3.MRL-Faslpr/J mice using a murine SLE model. C3.MRL-Faslpr/J mice were divided into saline (C), cyclophosphamide (Y), and ASC (H) treatment groups. Background-matched control C3H mice treated with saline (N) were also compared. The Y group showed the greatest improvement in disease parameters, but with damaged trabecular integrity. ASC transplantation reduced anti-dsDNA levels, glomerular C3 deposition and CD138 proportion significantly, without trabecular damage. Furthermore, both cyclophosphamide and ASC treatment significantly decreased the ratio of Th1/Th2 compared with the saline-treatment. The expression levels of miR-31-5p, miR-96-5p, miR-182-5p, miR-183-5p, and miR-379-5p were significantly higher, while those of miR150-5p were significantly lower in the C group than in the N group. The expression levels of miR-96-5p, miR-182-5p in the Y and H groups were significantly lower than in the C group. Thus, treatment with cyclophosphamide or ASC can change miRNAs and decrease miR-96-5p and miR-182-5p expression, as well as decreasing the CD138 proportion and the Th1/Th2 ratio, which might be involved in the therapeutic mechanism.

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“…Emerging evidence has demonstrated that miRNAs play a vital role in autoimmunity [14,15], and in LN in particular [16]. Recently, Liu et al demonstrated that miR-30a was significantly increased in B cells from SLE patients, and overexpressed miR-30a in vitro could lower the level of Lyn, a member of the Src family protein tyrosine kinases, in B cells [17].…”

Section: Pathogenesis Of Lupus Nephritismentioning

confidence: 99%

The pathogenesis, diagnosis and treatment of lupus nephritis

Schwartz

Goilav

Putterman

2014

Current Opinion in Rheumatology

114

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Purpose of review Renal involvement is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). In this review we provide an update on recent discoveries in the pathogenesis, diagnosis, and treatment of lupus nephritis (LN). Recent findings Localized long-lived plasma cells have been identified as playing an important role in LN. In addition, the roles of aberrant expression of microRNAs and pro-inflammatory cytokines have been explored. Early diagnosis is important for effective treatment and multiple biomarkers have been identified; however, none have been yet validated for clinical use. Biomarker panels may turn out to be more accurate than each individual component. Biologic agents for the treatment of LN are being studied, including Belimumab which was recently approved for non-renal SLE. Rituximab has not proven itself in large, placebo-controlled trials, although it is still being used in refractory cases of LN. Summary LN is a potentially devastating complication of SLE. Immune cells, cytokines, and epigenetic factors have all been recently implicated in LN pathogenesis. These recent discoveries may enable a paradigm shift in the treatment of this complex disease, allowing the tailoring of treatment to target specific pathogenic mediators at specific points in time in the progression of disease.

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MicroRNAs Implicated in the Immunopathogenesis of Lupus Nephritis

Cited by 32 publications

References 112 publications

Epigenetics and Systemic Lupus Erythematosus: Unmet Needs

Epigenetics and Systemic Lupus Erythematosus: Unmet Needs

Mesenchymal stem cell transplantation can restore lupus disease-associated miRNA expression and Th1/Th2 ratios in a murine model of SLE

The pathogenesis, diagnosis and treatment of lupus nephritis

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