We have shown previously that hypertension-related calcium-regulated gene (HCaRG) is involved in the control of renal cell proliferation and differentiation. To determine whether HCaRG plays a role in kidney repair after injury, we extended our studies on the cellular function of HCaRG by comparing cell migration of two kidney cell lines (HEK 293 and MDCK-C7) stably transfected with the plasmid alone or with a plasmid containing HCaRG cDNA. HCaRG expressing HEK 293 cells, which undergo lower proliferation, migrated faster than control cells and presented greater adhesiveness to the extracellular matrix. Faster migration was also observed for the MDKC-C7 cells, after stably transfecting them with HCaRG cDNA. HCaRG overexpression induced major morphological changes of HEK293 cells, including the formation of lamellipodia. Expression microarrays of HCaRG-expressing HEK293 cells revealed the elevated expression of several genes known to be involved in cell migration and lamellipodia formation, including transforming growth factor-alpha (TGF-), galectins, autotaxins and fibronectin. These cells exhibited augmented synthesis and release of activated TGF-. Conditioned medium from HCaRG-expressing cells stimulated the migration and induced significant morphological changes of control cells in part through activation of the TFG/EGF receptor. Altogether, these data support a role for HCaRG gene in kidney repair after injury through its effect on renal cell migration and TGF- secretion.