Tissue-Specific MicroRNA Expression Patterns in Four Types of Kidney Disease. J Am Soc Nephrol 2017 Oct;28(10):2985-2992
Date
07/01/2017Pubmed ID
28663230Pubmed Central ID
PMC5619963DOI
10.1681/ASN.2016121280Scopus ID
2-s2.0-85030470491 (requires institutional sign-in at Scopus site) 95 CitationsAbstract
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.
Author List
Baker MA, Davis SJ, Liu P, Pan X, Williams AM, Iczkowski KA, Gallagher ST, Bishop K, Regner KR, Liu Y, Liang MAuthor
Kevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BiomarkersCase-Control Studies
Humans
Kidney Diseases
Kidney Function Tests
Kidney Glomerulus
Kidney Tubules, Proximal
MicroRNAs
RNA, Messenger