Neuropeptide Y protects kidney from acute kidney injury by inactivating M1 macrophages via the Y1R-NF-κB-Mincle-dependent mechanism

Abstract

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.

Circulating neuropeptide Y as a biomarker in postoperative atrial fibrillation cases administered off-pump coronary bypass Graft surgery

“…However, the relationship between NPY and inflammation has been widely discussed. Lan and colleagues reported NPY deficiency inhibits inflammation in mice with experimental acute kidney injury and acute myocardial infarction by inactivating M1 macrophages [ 10 , 12 ]. In the central nervous system, NPY inhibits IL-1β and TNF-α production in microglial cells [ 25 ].…”

“…Neuropeptide Y (NPY, 36 amino acids), produced by brain and immune (macrophages and dendritic cells) cells, can activate sympathetic nerves [ [9] , [10] , [11] , [12] ]. Elevated NPY amounts were detected in myocardial infarction cases [ 13 ].…”

Plasma levels of neurogenic inflammation related neuropeptides in pediatric patients with community-acquired pneumonia and their potential diagnostic value in distinguishing viral and bacterial pneumonia

“…It is interesting that NPY levels were lower in patients with viral pneumonia in the current study. Publications on the association of low NPY levels with diseases are rare [ 30 , 31 ]. A study reported that when acute kidney injury develops, serum neuropeptide Y levels decrease rapidly in the early stage, and then it can protect the kidney by inhibiting macrophage activation [ 31 ].…”

“…Publications on the association of low NPY levels with diseases are rare [ 30 , 31 ]. A study reported that when acute kidney injury develops, serum neuropeptide Y levels decrease rapidly in the early stage, and then it can protect the kidney by inhibiting macrophage activation [ 31 ]. In the current study, the decrease in neuropeptide Y levels in viral pneumonia cases may be related to the decrease in this early stage.…”

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“…Furthermore, NPY is a 36-amino-acid peptide mostly produced by the nervous system and OCY ( 7 ). In acute kidney injury (AKI) mouse models, NPY exhibited renoprotective effects through Y1R by blocking M1 macrophage activation and renal necroinflammation ( 30 ). However, another cohort study pointed out that NPY was associated with proteinuria, faster CKD progression, and higher risk of kidney failure ( 31 ).…”