Unique miRNome and transcriptome profiles underlie microvascular heterogeneity in mouse kidney

Endothelial cells in blood vessels in the kidney exert different functions depending on the (micro)vascular bed they are located in. The present study aimed to investigate microRNA and mRNA transcription patterns that underlie these differences. We zoomed in on microvascular compartments in the 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 postcapillary venules. Quantitative RT-PCR, in situ hybridization, and immunohistochemistry were used to validate sequencing 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 postcapillary venules. Immunohistochemical staining showed that von Willebrand factor protein was mainly expressed in arterioles and postcapillary venules, whereas GABRB1 expression was enriched in glomeruli, and IGF1 was enriched in postcapillary venules. More than 550 compartment-specific microRNA-mRNA interaction pairs were identified that carry functional implications for microvascular behavior. In conclusion, our study identified unique microRNA and mRNA transcription patterns in microvascular compartments of the mouse kidney cortex that underlie microvascular heterogeneity. These patterns provide important molecular information for future studies into differential microvascular engagement in health and disease.NEW & NOTEWORTHY Renal endothelial cells display a high level of heterogeneity depending on the (micro)vascular bed they reside in. The molecular basis contributing to these differences is poorly understood yet of high importance to increase understanding of microvascular engagement in the kidney in health and disease. This report describes m(icro)RNA expression profiles of microvascular beds in the mouse renal cortex and uncovers microvascular compartment-specific m(icro)RNAs and miRNA-mRNA pairs, thereby revealing important molecular mechanisms underlying renal microvascular heterogeneity.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:325

Enthalten in:

American journal of physiology. Renal physiology - 325(2023), 3 vom: 01. Sept., Seite F299-F316

Sprache:

Englisch

Beteiligte Personen:

Luxen, Matthijs [VerfasserIn]
Zwiers, Peter J [VerfasserIn]
Meester, Femke [VerfasserIn]
Jongman, Rianne M [VerfasserIn]
Kuiper, Timara [VerfasserIn]
Moser, Jill [VerfasserIn]
Pultar, Marianne [VerfasserIn]
Skalicky, Susanna [VerfasserIn]
Diendorfer, Andreas B [VerfasserIn]
Hackl, Matthias [VerfasserIn]
van Meurs, Matijs [VerfasserIn]
Molema, Grietje [VerfasserIn]

Links:

Volltext

Themen:

Endothelial cells
Journal Article
MiRNome
MicroRNAs
Microvascular heterogeneity
RNA, Messenger
Renal microvascular compartments
Research Support, Non-U.S. Gov't
Transcriptome

Anmerkungen:

Date Completed 10.08.2023

Date Revised 22.09.2023

published: Print-Electronic

figshare: 10.6084/m9.figshare.21895842, 10.6084/m9.figshare.21593376

Citation Status MEDLINE

doi:

10.1152/ajprenal.00005.2023

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM359120245