Figure 2.

Schematic illustration of the Osteopontin signaling pathway and effects during obstructive nephropathy. UUO induces increased Angiotensin II (Ang II) levels which up-regulated Osteopontin (OPN) expression through AT1 receptor. This effect can be inhibited by statins. UUO also increases tubular expression of the CD44, a receptor of OPN. OPN actions may be mediated by uPAR, which reduces tubular apoptosis and interstitial fibrosis through reduced plasminogen activator inhibitor-1 (PAI-1) but promotes macrophage infiltration in the obstructive nephropathy. Discontinuous arrow connecting OPN and uPAR means that, although the relationship between them has been demonstrated "in vitro" (ref. 126 and 127), no direct relationship has been demonstrated in experimental or clinical models of obstructive nephropathy.