Transforming growth factor-beta 1 inhibits regeneration of renal proximal tubular cells after oxidant exposure.
Transforming growth factor-beta (TGF-beta), a regulatory cytokine expressed in the kidney, plays a role in nephrogenic repair. This study utilized a chemical model of renal proximal tubule cellular injury and regeneration to investigate the effects of TGF-beta 1 on regeneration. Confluent monolayers of rabbit renal proximal tubular cells (RPTC) in primary culture exposed to the oxidant t-butylhydroperoxide (800 microM TBHP) for 1.5 hours were 24% confluent after 24 hours. Confluency increased to 50% 4 days after TBHP exposure. Recovery of monolayer confluency was associated with increased monolayer protein but not with DNA content. Daily treatment of injured monolayers with TGF-beta 1 inhibited the recovery of monolayer confluency and inhibited recovery of protein content in a concentration-dependent manner (0.02-1 ng/mL). DNA content of injured monolayers was not altered by TGF-beta 1. A single treatment of injured monolayers with 0.2 ng/mL (8 pM) TGF-beta 1 inhibited recovery of monolayer confluency and protein content without altering monolayer DNA content. These data show that a single 24 hour exposure to a low concentration (8 pM) of TGF-beta 1 inhibits regeneration of renal proximal tubule cell monolayers following oxidative injury by inhibiting, in part, cellular migration/spreading.
Kays
S E
SE
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
Nowak
G
G
Schnellmann
R G
RG
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000293:injuries; D008956:Models, Chemical; D018384:Oxidative Stress; D010545:Peroxides / Q000633:toxicity; D011506:Proteins / Q000032:analysis / Q000378:metabolism; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000633:toxicity*; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D011506:Proteins; D016212:Transforming Growth Factor beta; D004247:DNA; D020122:tert-Butylhydroperoxide