Role of the heme oxygenase-adiponectin-atrial natriuretic peptide axis in renal function

The incidence of renal complications including kidney failure is on the rise. Moreover, with aging of the population and the high incidence of diabetes, hypertension and obesity, this trend may prevail. An important cytoprotective enzyme that has been shown to improve renal function is heme-oxygenase (HO). HO is known to abate apoptosis and necrosis, and improves cell vitality, which in turn, may enhance tissue regeneration. Consistently, HO has been shown to restore tissue morphology by potentiating potentiate proteins of repair/regeneration and promoting neovascularization. The formation of new tissue may replace damaged or dysfunctional tissue to preserve cellular integrity and function after injury. Emerging evidence indicate that HO-inducers improve kidney function in several models including, (i) streptozotocin-induced diabetic rats, (ii) Zucker-diabetic-fatty rats, (iii) Zucker-fatty rats, (iii) spontaneously hypertensive rats, (iv) uninephrectomized deoxycorticosterone-acetate hypertensive rats, (v) N(ω)-nitro-l-arginine-methyl ester (L-NAME)-induced hypertensive rats, (vi) glycerol induced renal failure, (vii) nephrotoxic nephritis, (viii) sepsis-induced kidney injury, (ix) cystic renal disease, (x) cisplatin-mediated acute kidney injury, and (xi) rhabdomyolysis-induced renal injury. The mechanisms underlying the HO-mediated reno-protection include: (i) the restoration of renal morphology by enhancing proteins of regeneration, (ii) the potentiation of the HO-adiponectin-atrial natriuretic peptide axis, with corresponding suppression of oxidative/inflammatory insults and extracellular matrix/profibrotic factors, and (iii) the potentiation of podocyte cytoskeletal proteins such as nephrin, podocin, podocalyxin and CD2-associated-protein, which are fundamental for forming the glomerular filtration barrier that selectively allows small molecules to pass through but not large protein molecules. Thus, this review highlights the HO-adiponectin-atrial natriuretic peptide axis in renoprotection.