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Peritubular capillary regression during the progression of experimental obstructive nephropathy
Ryuji Ohashi1, Akira Shimizu, Yukinari Masuda
1Department of Pathology, Nippon Medical School, Tokyo, Japan. rohashi@bcm.tmc.edu
Journal of the American Society of Nephrology : JASN
|June 29, 2002
Summary
Renal microvascular injury, specifically peritubular capillary (PTC) regression involving early angiogenesis and later apoptosis, contributes to tubulointerstitial scarring in kidney disease. This process is linked to vascular endothelial growth factor (VEGF) signaling changes.
Area of Science:
- Nephrology
- Vascular Biology
- Pathology
Background:
- Renal microvascular injury is implicated in progressive kidney disease.
- Peritubular capillary (PTC) disruption can lead to tubulointerstitial scarring, but the mechanisms are not fully understood.
Purpose of the Study:
- To investigate the morphological changes in PTC.
- To explore the role of vascular endothelial growth factor (VEGF) in regulating PTC during tubulointerstitial injury.
Main Methods:
- Unilateral ureteral obstruction model in Wistar rats.
- Immunohistochemistry for thrombomodulin (TM), VEGF, and Flk-1.
- Ki67 and TUNEL staining for cell proliferation and apoptosis.
- Electron microscopy and Western blotting.
Main Results:
- Early increase in tubular VEGF and PTC dilation, indicating an angiogenic response.
- Subsequent decrease in VEGF and Flk-1 expression, coupled with PTC regression and endothelial cell apoptosis.
- Significant reduction in PTC numbers correlated with tubulointerstitial scarring by week 4.
Conclusions:
- PTC regression, characterized by an initial angiogenic phase followed by apoptosis, is a key factor in tubulointerstitial scarring.
- VEGF signaling appears to play a critical, albeit transient, role in this process.