RETINOIC ACID REGULATION OF RENAL TUBULAR EPITHELIAL AND VASCULAR SMOOTH-MUSCLE CELL-FUNCTION

Vitamin A and its derivatives have been postulated to play an importan t role in renal tubulogenesis and compensatory hypertrophy. This study examined the effects of two carboxylic derivatives of vitamin A on Le wis lung carcinoma-porcine kidney-1 (LLC-PK1) renal tubular epithelial cell mito-and motogenesis and cell size. It was found that all-trans and 13-cis retinoic acids exerted modest, dose-dependent effects to st imulate incorporation of H-3-thymidine into acid-precipitable material of LLC-PK1 cells. The effects of all-trans retinoic acid to promote H -3-thymidine uptake in LLC-PK1 cells modestly enhanced that seen with acidic fibroblastic growth factor. Similar findings of these two retin oic acid derivatives to promote H-3-thymidine uptake and to enhance H- 3-thymidine uptake stimulated by another growth factor (platelet-deriv ed growth factor BB) were also observed in cultured bovine aortic smoo th muscle cells. Both retinoic acids promoted healing of denuded areas made within confluent monolayers of serum-starved LLC-PK1 cells. All- trans retinoic acid also stimulated recovery of mechanically denuded a reas within bovine aortic smooth muscle monolayers. Neither all-trans nor 13-cis retinoic acids affected cell size as assessed by forward li ght scatter with flow cytometry, suggesting lack of effect to induce h ypertrophy. These results demonstrate that two carboxylic acid derivat ives of vitamin A are capable of stimulation of basal and growth facto r-induced incorporation of H-3-thymidine uptake into acid-precipitable material and healing of denuded areas in disparate cell types. These findings are compatible with a role for vitamin A and its analogues in the tissue repair process.