TY - JOUR
T1 - Unique miRNome and transcriptome profiles underlie microvascular heterogeneity in mouse kidney
AU - Luxen, Matthijs
AU - Zwiers, Peter J
AU - Meester, Femke
AU - Jongman, Rianne M
AU - Kuiper, Timara
AU - Moser, Jill
AU - Pultar, Marianne
AU - Skalicky, Susanna
AU - Diendorfer, Andreas B
AU - Hackl, Matthias
AU - van Meurs, Matijs
AU - Molema, Grietje
N1 - Funding Information:
This project is cofinanced by the Ministry of Economic Affairs and Climate Policy by means of the PPP allowance made available by Top Sector Life Sciences & Health to stimulate public-private partnerships (No. 6334, to M.v.M. and G.M.). This work was also supported by a grant awarded by the Foundation De Cock-Hadders (No. 2020-55, to M.L.).
Publisher Copyright:
© 2023 The Authors.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - endothelial cells
KW - microvascular heterogeneity
KW - miRNome
KW - renal microvascular compartments
KW - transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85167482150&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00005.2023
DO - 10.1152/ajprenal.00005.2023
M3 - Article
C2 - 37410897
SN - 1931-857X
VL - 325
SP - F299-F316
JO - American journal of physiology-Renal physiology
JF - American journal of physiology-Renal physiology
IS - 3
ER -