Expression, roles, receptors, and regulation of osteopontin in the kidney

Osteopontin (OPN) is a secreted glycoprotein in both phosphorylated and non -phosphorylated forms. It contains an Arg-Gly-Asp cell-binding sequence and a thrombin-cleavage site. OPN is mainly present in the loop of Henle and d istal nephrons in normal kidneys in animals and humans. After renal damage, OPN expression may be significantly upregulated in all tubule segments and glomeruli. Studies utilizing OPN gene-deficient mice, antisense-treated or anti-OPN-treated animals have demonstrated that OPN promotes accumulation of macrophages, and may play a role in macrophage-mediated renal injury, bu t that the effect may be mild and short-lived. On the other hand, OPN has s ome renoprotective actions in renal injury, such as increasing tolerance to acute ischemia, inhibiting inducible nitric oxide synthase and suppressing nitric oxide synthesis, reducing cell peroxide levels and promoting the su rvival of cells exposed to hypoxia, decreasing cell apoptosis and participa ting in the regeneration of cells. In addition, OPN is associated with rena l stones, but whether it acts as a promoter or inhibitor of stone formation is controversial. It has been demonstrated that OPN receptors include two families: integrin and CD44. The OPN integrin receptors include alpha (V)be ta (3), alpha (V)beta (1), alpha (V)beta (5) and alpha (9)beta (1), and alp ha (4)beta (1). In normal human kidneys, standard CD44 is expressed most do minantly. Different OPN functions are mediated via distinct receptors. Para thyroid hormone, vitamin D-3, calcium, phosphate and some cytokines increas e OPN expression in vitro or in vivo, whereas female sex hormones and angio tensin-converting enzyme inhibitors or angiotensin II receptor antagonists decrease OPN expression in some renal damage states.