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Mechanical strain increases SPARC levels in podocytes: implications for glomerulosclerosis
Raghu V Durvasula1, Stuart J Shankland
1Division of Nephrology, Box 356521, Univ. of Washington School of Medicine, Seattle, WA 98195, USA. rdrvsula@u.washington.edu
American Journal of Physiology. Renal Physiology
|August 12, 2005
Summary
Mechanical stress on kidney podocytes increases secreted protein acidic and rich in cysteine (SPARC) levels. This finding suggests SPARC may mediate podocyte injury and contribute to glomerulosclerosis development.
Area of Science:
- Nephrology
- Cell Biology
- Pathophysiology
Background:
- Glomerular capillary hypertension is a key factor in glomerulosclerosis development.
- Podocyte injury and loss are early events in glomerulosclerosis.
- The mechanisms linking hypertension-induced podocyte injury are not fully understood.
Purpose of the Study:
- To investigate if mechanical strain activates secreted protein acidic and rich in cysteine (SPARC) in podocytes.
- To determine if SPARC mediates podocyte injury under conditions of glomerular capillary hypertension.
Main Methods:
- Conditionally immortalized mouse podocytes were subjected to cyclical stretch (mechanical strain).
- SPARC levels were measured in cell lysates and media.
- Immunostaining for SPARC was performed in spontaneously hypertensive rats.
Main Results:
- Cyclical stretch significantly increased SPARC levels in podocyte lysates and media.
- Increased SPARC levels in podocytes were observed in spontaneously hypertensive rats, a model of glomerular hypertension.
- The p38 pathway was identified as involved in the mechanical activation of SPARC.
Conclusions:
- Mechanical forces, such as those in glomerular capillary hypertension, increase SPARC levels in podocytes.
- Elevated SPARC may be a maladaptive response, contributing to podocyte loss and glomerulosclerosis progression.