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Published on: October 13, 2023
Intrarenal expression of microRNAs in patients with IgA nephropathy
Gang Wang1, Bonnie C-H Kwan, Fernand M-M Lai
1Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Abstract:
MicroRNAs (miRNAs) are noncoding, single-stranded RNA molecules that have important roles in a number of physiological and pathological processes. Previous studies have proved that miRNAs targeting ZEB1 and ZEB2 may repress epithelial-to-mesenchymal transition. In this work, we studied the intrarenal expression of miR-200 family, miR-205 and miR-192 in patients with immunoglobulin A (IgA) nephropathy. We studied 43 patients with biopsy-proven IgA nephropathy (IgA group). The intrarenal expression of miRNAs was quantified and compared with that of 15 patients with noninflammatory glomerulosclerosis (GS group) and 20 patients with nephrectomy for kidney cancer as controls (CTL group). The level of intrarenal miR-200c was downregulated, whereas the levels of intrarenal miR-141, miR-205 and miR-192 were upregulated in IgA but not GS group. Proteinuria significantly correlated with the intrarenal expression of miR-200c (r=-0.324, P=0.011) and glomerular filtration rate (GFR) significantly correlated with the intrarenal expression of miR-205 (r=-0.280, P=0.030). The degree of tubulointerstitial scarring correlated with miR-205 expression (r=0.389, P=0.021), whereas glomerulosclerosis correlated with miR-192 expression (r=-0.311, P=0.045). The rate of GFR decline significantly correlated with the intrarenal expression of miR-192 (r=0.373, P=0.015). The intrarenal expression of E-cadherin significantly correlated with the intrarenal expression of miR-200c (r=0.392, P=0.002). The results show that intrarenal expression of miR-200c, miR-141, miR-205 and miR-192 was diversely regulated and correlated with disease severity and progression in patients with IgA nephropathy. These miRNA species may be important in the pathogenesis and progression of IgA nephropathy.
Insights
In immunoglobulin A (IgA) nephropathy, specific microRNAs (miRNAs) like miR-200c, miR-141, miR-205, and miR-192 show altered expression. These miRNA changes correlate with disease severity and progression, suggesting a role in IgA nephropathy pathogenesis.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression involved in physiological and pathological processes.
- Previous research indicates that miRNAs targeting ZEB1 and ZEB2 can inhibit epithelial-to-mesenchymal transition, a process implicated in kidney fibrosis.
- The specific roles of intrarenal miRNAs in immunoglobulin A (IgA) nephropathy, a common cause of glomerulonephritis, remain incompletely understood.
Purpose of the Study:
- To investigate the intrarenal expression patterns of specific microRNAs (miR-200 family, miR-205, and miR-192) in patients with IgA nephropathy.
- To compare miRNA expression in IgA nephropathy patients with noninflammatory glomerulosclerosis and healthy controls.
- To determine the correlation between the expression of these miRNAs and clinical parameters, disease severity, and progression in IgA nephropathy.
Main Methods:
- Quantification of intrarenal miRNA expression (miR-200c, miR-141, miR-205, miR-192) in 43 IgA nephropathy patients, 15 glomerulosclerosis patients, and 20 controls.
- Analysis of correlations between miRNA levels and clinical data including proteinuria, glomerular filtration rate (GFR), tubulointerstitial scarring, and glomerulosclerosis.
- Assessment of the relationship between miRNA expression and E-cadherin levels, a marker of epithelial integrity.
Main Results:
- Intrarenal miR-200c was downregulated, while miR-141, miR-205, and miR-192 were upregulated in IgA nephropathy patients compared to controls.
- Proteinuria correlated with miR-200c levels, and GFR correlated with miR-205 levels.
- Tubulointerstitial scarring correlated with miR-205, glomerulosclerosis with miR-192, and GFR decline rate with miR-192. E-cadherin expression correlated with miR-200c.
Conclusions:
- Intrarenal expression of miR-200c, miR-141, miR-205, and miR-192 is differentially regulated in IgA nephropathy.
- These miRNAs are significantly associated with disease severity and progression markers in IgA nephropathy.
- The studied miRNAs may play a crucial role in the pathogenesis and advancement of IgA nephropathy.
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