Abstract
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN. In the context of IgAN, we aimed to analyze the role of miR-21-5p, miR-214-3p and miR-199a-5p, three established “fibromiRs” involved in renal fibrosis. Fifty-six IgAN biopsy specimens were retrospectively scored according to Oxford classification. Renal expression of miR-21-5p, miR-214-3p and miR-199a-5p were significantly associated with T score (miR-21-5p T0 RQ median = 1.23, T1 RQ = 3.01, T2 RQ = 3.90; miR-214-5p T0 RQ = 1.39, T1 RQ = 2.20, T2 RQ = 2.48; miR-199a-5p T0 RQ = 0.76, T1 RQ = 1.41, T2 RQ = 1.87). miR-21-5p expression was associated with S score (S0 RQ median = 1.31, S1 RQ = 2.65), but not miR-214-3p nor miR-199a-5p. In our cohort, poor renal survival was associated with high blood pressure, proteinuria and elevated creatininemia, as well as T and S scores. Moreover, renal expression of miR-21-5p, miR-214-3p were associated with renal survival. In conclusion, miR-21-5p, miR-214-3p and miR-199a-5p are three “fibromiRs” involved in renal fibrosis in the course of IgAN and miR-21-5p and miR-214-3p are associated with renal survival.
Highlights
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis leading to end stage renal disease (ESRD) in 20% to 40% of patients[1,2]
The histologic features of IgAN are diverse and include active lesions represented by mesangial hypercellularity, endocapillary and/or extra-capillary proliferation, as well as scarring lesions characterized by glomerular sclerosis and interstitial fibrosis[10]
As IgAN outcome is highly variable and difficult to predict between individuals, the identification of prognostic factors at the time of presentation is of major interest, especially if these markers represent targets for the development of anti-fibrotic therapeutics[7]
Summary
IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis leading to end stage renal disease (ESRD) in 20% to 40% of patients[1,2]. The histologic features of IgAN are diverse and include active lesions represented by mesangial hypercellularity, endocapillary and/or extra-capillary proliferation, as well as scarring lesions characterized by glomerular sclerosis and interstitial fibrosis[10]. The Oxford IgAN classification is a pathologic scoring system based on the pattern and the severity of both proliferative (mesangial and endocapillary hypercellularity) and scarring (segmental glomerular sclerosis and interstitial fibrosis) changes, and represents an established prognostic factor of IgAN11,12. Several experimental models have unraveled the implication of these miRNAs in various experimental models of tissue fibrosis[16,20,21] as well as fibroproliferative diseases[19] These miRNAs are consistently upregulated during fibrosis and represent prominent regulatory factors of TGFβ signaling, a major biological pathway driving fibrosis[17,22,23]. We evaluated for the first time the renal expression of three established “fibromiRs” (miR-21-5p, miR-199a-5p and miR-214-3p) in IgAN, as well as their association with Oxford classification, and renal survival
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