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Multilevel Microdissection and Functional-Structural Profiling of Human Renal Arterial Branches
Published on: September 5, 2025
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Maintenance of vascular integrity by pericytes is essential for normal kidney function
Dario R Lemos1, Graham Marsh1, Angela Huang1
1Research and Development, Biogen, Cambridge, Massachusetts.
American Journal of Physiology. Renal Physiology
|June 24, 2016
Summary
Kidney pericytes are crucial for maintaining kidney health. Their targeted removal caused acute kidney injury, highlighting their essential role in vascular support and overall kidney homeostasis.
Area of Science:
- Nephrology
- Vascular Biology
- Cell Biology
Background:
- Pericytes are mesenchymal progenitor cells associated with blood vessels and play a role in tissue regeneration.
- Kidney pericytes originate from FoxD1+ mesodermal progenitors during embryonic development.
Purpose of the Study:
- To investigate the necessity of kidney pericytes for maintaining postnatal kidney homeostasis.
- To determine the role of kidney pericytes in regulating microvascular function and kidney health.
Main Methods:
- Selective ablation of kidney pericytes in FoxD1Cre::RsDTR transgenic mice using diphtheria toxin.
- Assessment of kidney injury markers (creatinine, blood urea nitrogen, albuminuria).
- Analysis of tubular epithelial cell and endothelial cell changes, including lipid accumulation, mitochondrial swelling, apoptosis, and capillary loss.
- Pathway enrichment analysis of kidney pericyte gene expression.
- Recapitulation of human kidney peritubular capillaries in microphysiological devices.
Main Results:
- Selective pericyte ablation (>90%) led to acute kidney injury within 96 hours.
- Loss of pericytes resulted in tubular epithelial cell damage (lipid vacuoles, swollen mitochondria, apoptosis) and endothelial cell dysfunction (swelling, reduced vascular homeostasis markers, capillary loss).
- No acute inflammatory response was observed post-ablation.
- Kidney pericyte gene expression implicated basement membrane proteins, angiogenic factors, and vascular tone regulators.
- In vitro models confirmed pericytes regulate capillary permeability, basement membrane deposition, and microvascular tone.
Conclusions:
- Kidney pericytes are essential for maintaining adult kidney homeostasis.
- Pericytes actively support the microvasculature, regulating its function and integrity.
- Targeting kidney pericytes offers a potential avenue for understanding and treating kidney diseases.
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