Publications (2)7.36 Total impact
-
Article: HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
[show abstract] [hide abstract]
ABSTRACT: We have shown previously that the hypertension-related, calcium-regulated gene (HCaRG) is involved in the control of renal cell proliferation and differentiation (Devlin AM, Solban N, Tremblay S, Gutkowska J, Schurch W, Orlov SN, Lewanczuk R, Hamet P, and Tremblay J. Am J Physiol Renal Physiol 284: F753-F762, 2003). 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 [HEK293 and Madin-Darby canine kidney (MDCK)-C7] stably transfected with the plasmid alone or with a plasmid containing HCaRG cDNA. HCaRG-expressing HEK293 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 MDCK-C7 cells, after they were stably transfected with HCaRG cDNA. HCaRG overexpression induced major morphological changes in 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-alpha), galectins, autotaxins and fibronectin. These cells exhibited augmented synthesis and release of activated TGF-alpha. Conditioned medium from HCaRG-expressing cells stimulated the migration and induced significant morphological changes in control cells, in part, through activation of the TFG-alpha/EGF receptor. Together, these data support a role for HCaRG in kidney repair after injury through its effect on renal cell migration and TGF-alpha secretion.American journal of physiology. Renal physiology 01/2006; 289(6):F1273-80. · 3.68 Impact Factor -
Article: HCaRG is a novel regulator of renal epithelial cell growth and differentiation causing G2M arrest.
[show abstract] [hide abstract]
ABSTRACT: We recently identified a novel calcium-regulated gene, HCaRG, that is highly expressed in the kidney and maps to a chromosomal locus determining kidney weight in rats. The mRNA levels of HCaRG negatively correlate with the proliferative status of the kidney cells. To investigate its role in renal epithelial cellular growth directly, we studied the human embryonic kidney cell line (HEK-293) stably transfected with either plasmid alone or plasmid containing rat HCaRG. [(3)H]thymidine incorporation was significantly lower in HCaRG clones. Although HCaRG clones exhibited some enhanced susceptibility to cell death, this was not the primary mechanism of reduced proliferation. Cell cycle analysis revealed a G(2)M phase accumulation in HCaRG clones that was associated with upregulation of p21(Cip1/WAF1) and downregulation of p27(Kip1). HCaRG clones had a greater protein content, larger cell size, and released 4.5- to 8-fold more of an atrial natriuretic peptide-like immunoreactivity compared with controls. In addition, HCaRG clones demonstrated the presence of differentiated junctions and a lower incidence of mitotic figures. Genistein treatment of wild-type HEK-293 cells mimicked several phenotypic characteristics associated with HCaRG overexpresssion, including increased cell size and increased release of atrial natriuretic peptide. Taken together, our results suggest that HCaRG is a regulator of renal epithelial cell growth and differentiation causing G(2)M cell cycle arrest.American journal of physiology. Renal physiology 05/2003; 284(4):F753-62. · 3.68 Impact Factor
