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

Abstract

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 distal nephrons in normal kidneys in animals and humans. After renal damage, OPN expression may be significantly up-regulated 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, but that the effect may be mild and short-lived. On the other hand, OPN has some 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 survival of cells exposed to hypoxia, decreasing cell apoptosis and participating in the regeneration of cells. In addition, OPN is associated with renal 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)beta(3), alpha(v)beta(1), alpha(v)beta(5) and alpha(9)beta(1), and alpha(4)beta(1). In normal human kidneys, standard CD44 is expressed most dominantly. Different OPN functions are mediated via distinct receptors. Parathyroid hormone, vitamin D(3), calcium, phosphate and some cytokines increase OPN expression in vitro or in vivo, whereas female sex hormones and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists decrease OPN expression in some renal damage states.

Midkine is involved in tubulointerstitial inflammation associated with diabetic nephropathy

“…15 In addition, reduction of osteopontin expression in Mdk À/À mice is also important, because not only MCP-1 but also osteopontin is known to promote macrophage accumulation. 31 Our study revealed the source of MK expression, namely TEC and macrophages. MCP-1 expression is also induced in these cells, as shown in this study as well as in previous reports including one reporting MCP-1 induction in TEC in vivo in STZ-induced diabetes models.…”

Osteopontin is an endogenous modulator of the constitutively activated phenotype of pulmonary adventitial fibroblasts in hypoxic pulmonary hypertension

“…In several disease states (pulmonary fibrosis, myocardial infarction, experimental models of renal injury, certain forms of PH), tissue fibroblasts have been shown to display highly migratory and even proinvasive properties similar to those of metastatic cancer cells (30,42,66,68). Vascular adventitial fibroblasts with an activated phenotype have been shown to invade vascular matrix and migrate to the medial and even intimal vessel wall layers (47,51,52).…”

Detection of osteopontin on Holstein bull spermatozoa, in cauda epididymal fluid and testis homogenates, and its potential role in bovine fertilization

“…More recently it has been detected in many tissues and fluids, including urine (Sorenson et al 1995), milk (Sorensen & Petersen 1993, Sorensen et al 2003, kidney (Xie et al 2001), uterine endometrium of rabbits (Apparao et al 2003), sheep (Johnson et al 2003, Kimmins et al 2004, cows (Kimmins et al 2004) and pigs (Garlow et al 2002), the bovine oviduct (Gabler et al 2003), and on the luminal surfaces of epithelial cells of human gastrointestinal and reproductive tracts, gall bladder, pancreas, lung, breast, urinary tract, salivary glands, and sweat glands (Brown et al 1992). OPN may be glycosylated, phosphorylated and sulfated, and its expression and post-translational modifications are tissue-specific and regulated by many hormones and growth factors (Denhardt & Guo 1993).…”