Hepatocyte growth factor (HGF) is a potent
renotropic factor that has been shown to play important roles in kidney development and recovery from
acute renal injury. To examine the effects of HGF on renal tubular epithelium, we generated HGF-producing renal epithelial cells by stably transfecting mIMCD-3 and OK cells with an expression plasmid containing human HGF
cDNA. Expression of HGF in the transfected cells was confirmed by detection of HGF
mRNA by Northern blot analysis and detection of HGF secretion into the
conditioned medium by ELISA. HGF-transfected cells exhibited fibroblast-like scattered morphology and increased cell motility. They formed branching tubules when grown in 3-D
collagen gel. In addition, HGF-producing cells grew faster than their parental cells, but failed to form colonies in soft
agar. These phenotypic changes were inhibited by a specific, neutralizing anti-HGF antibody. Interestingly, both c-met transcript and c-met
protein were increased in HGF-transfected cells, suggesting that HGF amplifies its own action via stimulation of c-met expression. Autocrine expression of HGF and c-met in renal epithelial cells also stimulated
fibronectin gene expression, which was totally blocked by incubation with a neutralizing anti-HGF but not a pan-specific anti-
TGF-beta antibody, suggesting that it is independent of
TGF-beta production. Our data demonstrate that HGF as a single factor stimulates renal epithelial cell proliferation, migration, differentiation, and extracellular matrix remodeling, making it uniquely suited to promote renal tubulogenesis during development, as well as to reconstitute tubular integrity following acute injury.