REGENERATION OF RENAL PROXIMAL TUBULE CELLS IN PRIMARY CULTURE FOLLOWING TOXICANT INJURY - RESPONSE TO GROWTH-FACTORS

Growth factors may play an important role in the repair of the renal p roximal tubule epithelium following toxic injury. This study investiga ted the regeneration of rabbit renal proximal tubule cell (RPTC) monol ayers following exposure to the nephrotoxicants tert-butylhydroperoxid e (TBHP) and 1,2-dichlorovinyl-L-cysteine (DCVC), and the effect of ex ogenous growth factors on the regeneration process. Confluent monolaye rs exposed to TBHP or DCVC for 1.5-2 hr were 23 and 43% confluent, res pectively, after 24 hr. Confluency increased to 63 and 80% 4 days afte r TBHP or DCVC exposure, but decreased to 29 and 24% after 8 days. Mon olayer DNA content did not increase after TBHP or DCVC exposure; howev er, monolayer protein/DNA ratio increased above control values after D CVC exposure. Recovery of confluency was not sensitive to RGD-containi ng peptides that inhibit the binding of integrins to extracellular mat rix. Epidermal growth factor (EGF) treatment resulted in complete reco very of confluency, and protein and DNA contents 4-6 days after injury . Unlike EGF, IGF-1 or insulin treatment produced a small increase in confluency following TBHP exposure. These results suggest that hypertr ophy following DCVC exposure and migration/spreading after TBHP and DC VC exposure play a partial and temporary role in the regeneration of R PTC monolayers, that in the absence of exogenous growth factors prolif eration and complete regeneration of the monolayer does not occur, tha t toxicants may alter the production of mitogenic factors, and that EG F is a potent and efficacious growth factor in promoting regeneration. (C) 1995 Academic Press, Inc.