Mechanisms of recovery from mechanical injury of renal tubular epithelial cells.
The mechanism(s) whereby a denuded renal tubular epithelial cell surface becomes reestablished remains unknown. We therefore measured the rate 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 reduced indexes of proliferation (5-bromo-2'-deoxyuridine and thymidine uptake) without affecting wound healing. Serum and epidermal growth factor (EGF) enhance whereas transforming growth factor-beta 1 (TGF-beta 1) impairs wound healing. Hepatocyte growth factor (HGF) stimulates wound healing at low concentrations and inhibits healing at high concentrations 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) did not affect wound healing in either cell type. Healing of LLC-PK1 but not MDCK cells was impaired by exposure to a peptide containing a RGD sequence. Conversely, healing of MDCK but not LLC-PK1 cells was impaired by the REDV tetrapeptide. Healing of both LLC-PK1 and MDCK was impaired by heparin but not by the LDVPS peptide. These results demonstrate 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sponsel
H T
HT
Department of Medicine, Denver Veterans Affairs Medical Center, Colorado.
Breckon
R
R
Hammond
W
W
Anderson
R J
RJ
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D002455:Cell Division / Q000528:radiation effects; D002460:Cell Line; D002465:Cell Movement; D016384:Consensus Sequence; D016207:Cytokines / Q000494:pharmacology; D004848:Epithelium / Q000293:injuries / Q000473:pathology / Q000528:radiation effects; D006133:Growth Substances / Q000494:pharmacology; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000293:injuries* / Q000473:pathology / Q000528:radiation effects; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D006133:Growth Substances; D016023:Integrins; D013936:Thymidine