neuropeptide-y and Acute-Kidney-Injury

Neuropeptide Y (NPY) is produced by the nerve system and may contribute to the progression of CKD. The present study found the new protective role for NPY in AKI in both patients and animal models. Interestingly, NPY was constitutively expressed in blood and resident kidney macrophages by co-expressing NPY and CD68+ markers, which was lost in patients and mice with AKI-induced by cisplatin. Unexpectedly, NPY was renoprotective in AKI as mice lacking NPY developed worse renal necroinflammation and renal dysfunction in cisplatin and ischemic-induced AKI. Importantly, NPY was also a therapeutic agent for AKI because treatment with exogenous NPY dose-dependently inhibited cisplatin-induced AKI. Mechanistically, NPY protected kidney from AKI by inactivating M1 macrophages via the Y1R-NF-κB-Mincle-dependent mechanism as deleting or silencing NPY decreased Y1R but increased NF-κB-Mincle-mediated M1macrophage activation and renal necroinflammation, which were reversed by addition of NPY or by silencing Mincle but promoted by blocking Y1R with BIBP 3226. Thus, NPY is renoprotective and may be a novel therapeutic agent for AKI. NPY may act via Y1R to protect kidney from AKI by blocking NF-κB-Mincle-mediated M1 macrophage activation and renal necroinflammation.

Topics: Acute Kidney Injury; Animals; Cisplatin; Kidney; Macrophages; Mice; Neuropeptide Y; NF-kappa B; Receptors, Neuropeptide Y

Changes of catecholamine and neuropeptide Y (NPY) were investigated in experimental acute renal failure (ARF) of rats. Concentrations of noradrenaline (NA) and dopamine (DA) were determined by chromatographic analysis using electrochemical detection. Renal content of NPY, identified by radioimmunoassay, was expressed as NPY-like immunoreactivity (NPY-LI). All animals with a plasma urea value higher than 200 mg/dl induced by injection of glycerol were employed as ARF subjects for the experiment. Formation of ARF was also confirmed by histological findings showing diffused necrosis of tubular epithelia. In ARF rats, renal contents of NA and DA decreased markedly (P less than 0.001), NA (ng/g wet tissue) decreased from 186.3 +/- 19.6 to 2.81 +/- 0.67 (n = 8), and DA (ng/g wet tissue) decreased from 14.69 +/- 4.97 to 4.05 +/- 2.66 (n = 8). Similarly, NPY-LI (pg/g wet tissue) in ARF was reduced significantly (P less than 0.001) from 435.23 +/- 35.82 to 4.61 +/- 0.52 (n = 8). The decrease of NA in ARF was obtained parallel to the change of NPY-LI; degeneration of adrenergic nerve fibers was confirmed by immunohistochemical observation. Results obtained suggest damage to the adrenergic and the dopaminergic innervation in the kidneys during ARF.

Topics: Acute Kidney Injury; Animals; Dopamine; Female; Glycerol; Male; Neuropeptide Y; Norepinephrine; Rats; Rats, Inbred Strains