MECHANISMS OF RECOVERY FROM MECHANICAL INJURY OF RENAL TUBULAR EPITHELIAL-CELLS

The mechanism(s) whereby a denuded renal tubular epithelial cell surfa ce becomes reestablished remains unknown. We therefore measured the ra te of renewal of mechanical wounds made in confluent monolayers of two established renal tubular epithelial cell lines. We found that wounds of MDCK cells heal at a faster rate than wounds of LLC-PK1 cells. The magnitude of wound healing did not differ when cells grown on plastic were compared with cells grown on fibronectin, laminin, or collagen. Irradiation (4,000 rads) of MDCK and LLC-PK1 cells significantly reduc ed indexes of proliferation (5-bromo-2'-deoxyuridine and thymidine upt ake) without affecting wound healing. Serum and epidermal growth facto r (EGF) enhance whereas transforming growth factor-pi (TGF-beta 1) imp airs wound healing. Hepatocyte growth factor (HGF) stimulates wound he aling at low concentrations and inhibits healing at high concentration s in MDCK cells while not affecting healing of LLC-PK1 cell wounds at any concentration. Several interleukins (IL-1, IL-2, IL-3, and IL-6) d id not affect wound healing in either cell type. Healing of LLC-PK1 bu t not MDCK cells was impaired by exposure to a peptide containing a RG D sequence. Conversely, healing of MDCK but not LLC-PK1 cells was impa ired by the REDV tetrapeptide. Healing of both LLC-PK1 and MDCK was im paired by heparin but not by the LDVPS peptide. These results demonstr ate that mechanical wounds of LLC-PK1 and MDCK cells heal, at least in part, by migration. Healing is regulated by serum and growth factors including EGF, HGF, and TGF-beta 1. The RGD sequence appears to be an important mediator of LLC-PK1 cell healing, whereas the REDV sequence appears important in MDCK cell healing. A heparin-sensitive site is an important contributor in healing of both LLC-PK1 and MDCK cells.