The long term goal of this research is to understand how the kidney recovers from a xenobiotic insult though cell repair and regeneration. Numerous xenobiotics such as halocarbons and oxidants produce nephrotoxicity through renal proximal tubule cellular (RPTC) injury and death. The kidney can recover from renal failure through repair and regeneration of the non-injured and sublethally-injured RPTC; though the mechanisms of repair and regeneration are poorly understood. Recently, in vitro models of cell repair and regeneration using primary cultures of rabbit RPTC have been developed, and differences observed in the ability of injured RPTC to repair cellular functions and regenerate following exposure to the nephrotoxic halocarbon dichlorovinyl-L- cysteine (DCVC) and the oxidant t-butylhydroperoxide (TBHP). Extracellular matrix (ECM)-integrin interactions play a critical role in cell attachment and in triggering/transducing signals for cell proliferation and functions. Collagens are important ECM proteins and preliminary studies demonstrate that TBHP alters collagen Type IV mRNA expression in RPTC. The central hypothesis of this proposal is that repair of physiological functions and regeneration of RPTC following sublethal injury is dependent on the re-establishment of collagen production and collagen binding integrin levels and localization on the plasma membrane.
Specific Aim I will determine the role of collagens I and IV in the promotion of RPTC physiological functions.
Specific AIM II will determine the role of collagens and collagen binding integrins in the promotion of proliferation and repair of membrane polarity and physiological functions in RPTC following TBHP exposure.
Specific AIM III will determine the role of collagens and collagen binding integrins in the lack of RPTC repair and regeneration following DCVC exposure. Completion of these aims will result in a better understanding of the mechanisms involved in renal cell regeneration and the repair of physiological functions following toxicant exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
7R01ES004410-12
Application #
6467560
Study Section
Special Emphasis Panel (ZRG4-HPD (02))
Program Officer
Mastin, Patrick
Project Start
1987-07-01
Project End
2002-12-31
Budget Start
2001-08-10
Budget End
2001-12-31
Support Year
12
Fiscal Year
2001
Total Cost
$194,104
Indirect Cost
Name
Medical University of South Carolina
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425