Pro-Angiogenic and Antimesangioproliferative Effects

]) gene isreduced before the proliferative phase and increasedin glomeruli and serum when mesangial cell prolifer-ation subsides. To further elucidate its role in mesan-gioproliferative glomerulonephritis, CCN3 systemi-cally was overexpressed by muscle electroporation inhealthy or nephritic rats. This increased CCN3 serumconcentrations more than threefold for up to 56 days.At day 5 after disease induction, CCN3-transfected ratsshowed an increase in glomerular endothelial areaand in mRNA levels of the pro-angiogenic factors vas-cular endothelial growth factor and PDGF-C. At day 7,CCN3 overexpression decreased mesangial cell prolif-eration, including expression of -smooth muscle ac-tin and matrix accumulation of fibronectin and typeIV collagen. In progressive nephritis (day 56), over-expression of CCN3 resulted in decreased albumin-uria, glomerulosclerosis, and reduced cortical colla-gen type I accumulation. In healthy rat kidneys,overexpression of CCN3 induced no morphologicchanges but regulated glomerular gene transcripts(reduced transcription of PDGF-B, PDGF-D, PDGF-re-ceptor– , and fibronectin, and increased PDGF-recep-tor– and PDGF-C mRNA). These data identify a dualrole for CCN3 in experimental glomerulonephritiswith pro-angiogenic and antimesangioproliferativeeffects. Manipulation of CCN3 may represent a novelapproach to help repair glomerular endothelial dam-age and mesangioproliferative changes.