Tissue-Specific MicroRNA Expression Patterns in Four Types of Kidney Disease

Abstract

MicroRNAs contribute to the development of kidney disease. Previous analyses of microRNA expression in human kidneys, however, were limited by tissue heterogeneity or the inclusion of only one pathologic type. In this study, we used laser-capture microdissection to obtain glomeruli and proximal tubules from 98 human needle kidney biopsy specimens for microRNA expression analysis using deep sequencing. We analyzed specimens from patients with diabetic nephropathy (DN), FSGS, IgA nephropathy (IgAN), membranoproliferative GN (MPGN) (n=19-23 for each disease), and a control group (n=14). Compared with control glomeruli, DN, FSGS, IgAN, and MPGN glomeruli exhibited differential expression of 18, 12, two, and 17 known microRNAs, respectively. The expression of several microRNAs also differed between disease conditions. Specifically, compared with control or FSGS glomeruli, IgAN glomeruli exhibited downregulated expression of hsa-miR-3182. Furthermore, in combination, the expression levels of hsa-miR-146a-5p and hsa-miR-30a-5p distinguished DN from all other conditions except IgAN. Compared with control proximal tubules, DN, FSGS, IgAN, and MPGN proximal tubules had differential expression of 13, 14, eight, and eight microRNAs, respectively, but expression of microRNAs did not differ significantly between the disease conditions. The abundance of several microRNAs correlated with indexes of renal function. Finally, we validated the differential glomerular expression of select microRNAs in a second cohort of patients with DN (n=19) and FSGS (n=21). In conclusion, we identified tissue-specific microRNA expression patterns associated with several kidney pathologies. The identified microRNAs could be developed as biomarkers of kidney diseases and might be involved in disease mechanisms.

Keywords: biopsy; chronic kidney disease; glomerulus; kidney; microRNA; proximal tubule.

Figure 1.

Several microRNAs are differentially expressed in the glomeruli between controls and each type of kidney disease. (A) DN. (B) MPGN. (C) FSGS. (D) IgAN. Log₂ fold changes of each disease over controls for microRNAs with FDR<0.05 are shown.

Figure 2.

Several microRNAs are differentially expressed in the glomeruli between different types of kidney disease. (A) FSGS compared with DN. (B) MPGN compared with DN. (C) IgAN compared with FSGS. (D) MPGN compared with FSGS. (E) MPGN compared with IgAN. Log₂ fold changes for microRNAs with FDR<0.05 are shown.

Figure 3.

Several microRNAs are differentially expressed in the proximal tubules between controls and each type of kidney disease. (A) DN. (B) MPGN. (C) FSGS. (D) IgAN. Log₂ fold changes of each disease over controls for microRNAs with FDR<0.05 are shown.

Figure 4.

Differential expression of select miRNAs was validated in a second cohort of patients. (A) Abundance of miR-146a-5p and miR-24-3p in glomerular samples from additional patients with DN and FSGS on the basis of qPCR analysis. (B) Log₂ fold differences of FSGS/DN from microRNA-sequencing analysis of original samples and qPCR analysis of new validation samples. *P<0.05; P=0.17 for miR-24-3p.