Figure 4.

Strategy to identify nephron segment-specific urinary microRNAs (miRNAs) within a cross-laboratory research program conducted by the Health and Environmental Sciences Institute Biomarkers of Nephrotoxicity Committee. Rats were treated with nephron segment selective toxicants causing injury to glomeruli, proximal tubules, Henle’s loops, and collecting ducts. Urinary miRNAs were profiled by quantitative polymerase chain reaction (qPCR). A meta-analysis was then performed to identify significantly modulated urinary miRNAs that were common and/or specific across studies. Given that some compounds produced a mixture of lesions in several nephron segments, small RNA sequencing and other confirmatory experiments were conducted in nephron segments isolated by laser capture microdissection (LCM) to further characterize the localization of miRNA candidates.