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Effect on innate immunity of glomerular and tubular cells prolonged exposure to mechanical stretching

Grant number: 13/00721-0
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): May 01, 2013
Effective date (End): August 31, 2017
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Roberto Zatz
Grantee:Simone da Costa Alarcon Arias
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/10926-5 - Pathogenesis and treatment of chronic kidney disease: role of innate immunity in glomerular, tubular and interstitial injury, AP.TEM


Mechanical stretch - resulting from hypertension and/or glomerular hypertrophy - represents one of the most important non immunological mechanisms of chronic glomerular injury, occurring in situations such as diabetic nephropathy and focal segmental glomerulosclerosis, and contributing to the perpetuation of any nephropathy in which the number of nephrons is substantially reduced. Several in vitro observations suggest that cultured glomerular cells subjected to mechanical stretching react by increasing their proliferation rate as well as their synthesis of inflammatory mediators, such as TGF-beta, cyclooxygenase derivatives and adhesion molecules. The discovery of this effect, observed with the three major cell types present in the glomeruli - endothelial cells, mesangial cells and podocytes - helped to clarify the connection between the mechanical aggression to the glomeruli and the development of CKD. However, several key aspects of this relationship remain unclear. Which one(s) of the intracellular mechanism(s) promotes the translation of the mechanical stimuli into the production of inflammatory mediators? What is the contribution of each cell type to that process? Is there a molecular pattern of response to the stretching that can be recognized in each of the cells involved and/or in the glomeruli as a whole? Do tubular epithelial cells respond to such stimuli in the same way as glomerular cells? (If this is the case, it will be easier to explain the inflammatory process associated with obstructive nephropathy). Finally, does the transduction of mechanical stretch to a proinflammatory phenotype involve participation of the innate immunity?

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