Collagen IV promotes repair of renal cell physiological functions after toxicant injury.
Collagen IV is found in the renal proximal tubular cell (RPTC) basement membrane and is a mediator of renal development and function. Pharmacological concentrations of L-ascorbic acid phosphate (AscP) promote the repair of physiological functions in RPTC sublethally injured by S-(1,2-dichlorovinyl)-L-cysteine (DCVC). We hypothesized that AscP promotes RPTC repair by stimulating collagen IV synthesis and/or deposition. RPTC exhibited increased synthesis but decreased deposition of collagen IV after DCVC exposure. In contrast, RPTC cultured in pharmacological concentrations of AscP maintained collagen IV deposition. The activity of prolyl hydroxylase was decreased in RPTC after DCVC injury, an effect that was partially attenuated in injured RPTC cultured in pharmacological concentrations of AscP. The addition of exogenous collagen IV to the culture media of DCVC-injured RPTC promoted the repair of mitochondrial function and Na(+)-K(+)-ATPase activity. However, neither collagen I, laminin, nor fibronectin promoted cell repair. These data demonstrate an association between AscP-stimulated deposition of collagen IV and exogenous collagen IV and repair of physiological functions, suggesting that collagen IV plays a specific role in RPTC repair after sublethal injury.
Nony
P A
PA
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA.
Nowak
G
G
Schnellmann
R G
RG
D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D001485:Basement Membrane / Q000502:physiology; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000502:physiology*; D003545:Cysteine / Q000031:analogs & derivatives / Q000633:toxicity*; D005260:Female; D006909:Hydroxyproline / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D010101:Oxygen Consumption / Q000187:drug effects; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
C017028:ascorbate-3-phosphate; C039961:S-(1,2-dichlorovinyl)cysteine; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D000254:Sodium-Potassium-Exchanging ATPase; D003545:Cysteine; D001205:Ascorbic Acid; D006909:Hydroxyproline