Unique miRNome and transcriptome profiles underlie microvascular heterogeneity in mouse kidney

BACKGROUND Endothelial cells in the blood vessels in the kidney exert different functions depending on the (micro)vascular bed they are located in. The current study aimed to investigate microRNA and mRNA transcription patterns that underlie these differences. METHODS We zoomed in on the microvascular compartments in mouse renal cortex by laser microdissecting the microvessels prior to small RNA and RNA sequencing analyses. By these means, we characterized microRNA and mRNA transcription profiles of arterioles, glomeruli, peritubular capillaries, and post-capillary venules. RT-qPCR, in situ hybridization, and immunohistochemistry were used to validate sequencing results. RESULTS Unique microRNA and mRNA transcription profiles were found in all microvascular compartments, with dedicated marker microRNAs and mRNAs showing enriched transcription in a single microvascular compartment. In situ hybridization validated the localization of microRNAs mmu-miR-140-3p in arterioles, mmu-miR-322-3p in glomeruli, and mmu-miR-451a in post-capillary venules. Immunohistochemical staining showed that von Willebrand Factor protein was mainly expressed in arterioles and post-capillary venules, while GABRB1 expression was enriched in glomeruli and IGF1 in post-capillary venules. More than 550 compartment-specific microRNA-mRNA interaction pairs were identified that carry functional implications for microvascular behavior. CONCLUSION Our study identified unique microRNA and mRNA transcription patterns in microvascular compartments of mouse kidney cortex which underlie microvascular heterogeneity. These patterns provide important molecular information for future studies into differential microvascular engagement in health and disease. ntified profiles provide important molecular information to take into account for future studies into microvascular engagement in health and disease.