Parathyroid hormone-related protein interacts with vascular endothelial growth factor to promote fibrogenesis in the obstructed mouse kidney.

Parathyroid hormone-related protein (PTHrP) interacts with vascular endothelial growth factor (VEGF) in osteoblasts. Since both PTHrP and VEGF have both proinflammatory and profibrogenic features, we assessed here whether these factors might act in concert to promote fibrogenesis in the obstructed kidney. VEGF receptor (VEGFR)-1 was upregulated, while VEGFR-2 was downregulated (at both mRNA and protein levels) in the mouse kidney within 2–6 days after ureteral obstruction. VEGF protein levels also increased in the obstructed kidney at the latter time. Moreover, this VEGF and VEGFR-1 upregulation was higher in mice overexpressing PTHrP in the proximal tubule than in control littermates. These changes were associated with higher fibronectin mRNA expression and α-smooth muscle actin (α-SMA) and integrin-linked kinase (ILK) immunostaining and lower apoptotic tubulointerstitial cells in the mouse obstructed kidney than in control littermates. Pretreatment with a neutralizing anti-VEGF antibody reversed these r...