Extracellular renalase protects cells and organs by outside‐in signalling

Wang, Yang; Safirstein, Robert; Velázquez, Heino; Guo, Xiaojia; Hollander, Lindsay; Chang, John; Chen, Tian-Min; Mu, Jianjun; Desir, Gary V.

doi:10.1111/jcmm.13062

Cited by 39 publications

(81 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…M2 macrophages are associated with wound healing, tissue repair, and tumor promotion. In the context of cancer, we have suggested that dysregulated RNLS signaling could bias macrophages to an M2-like phenotype (13). We have also found that RNLS suppresses inflammasome activity in stimulated macrophages.…”

Section: Renalase Reduces Experimental Pancreatitismentioning

confidence: 82%

The serum protein renalase reduces injury in experimental pancreatitis

Kolodecik

Reed

Date

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Acute pancreatitis is a disease associated with inflammation and tissue damage. One protein that protects against acute injury, including ischemic injury to both the kidney and heart, is renalase, which is secreted into the blood by the kidney and other tissues. However, whether renalase reduces acute injury associated with pancreatitis is unknown. Here, we used both and murine models of acute pancreatitis to study renalase's effects on this condition. In isolated pancreatic lobules, pretreatment with recombinant human renalase (rRNLS) blocked zymogen activation caused by cerulein, carbachol, and a bile acid. Renalase also blocked cerulein-induced cell injury and histological changes. In the cerulein model of pancreatitis, genetic deletion of renalase resulted in more severe disease, andadministering rRNLS to cerulein-exposed WT mice after pancreatitis onset was protective. Because pathological increases in acinar cell cytosolic calcium levels are central to the initiation of acute pancreatitis, we also investigated whether rRNLS could function through its binding protein, plasma membrane calcium ATPase 4b (PMCA4b), which excretes calcium from cells. We found that PMCA4b is expressed in both murine and human acinar cells and that a PMCA4b-selective inhibitor worsens pancreatitis-induced injury and blocks the protective effects of rRNLS. These findings suggest that renalase is a protective plasma protein that reduces acinar cell injury through a plasma membrane calcium ATPase. Because exogenous rRNLS reduces the severity of acute pancreatitis, it has potential as a therapeutic agent.

show abstract

Section: Renalase Reduces Experimental Pancreatitismentioning

confidence: 82%

The serum protein renalase reduces injury in experimental pancreatitis

Kolodecik

Reed

Date

et al. 2017

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…31 The level of renalase secreted into the blood is determined by renal function, renal perfusion and circulating catecholamine levels. 32 In patients with primary hypertension, serum renalase level was associated with elevated blood pressure. 33 However, no association has been reported between plasma renalase level and blood pressure in healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Levels of Serum and Urine Catecholaminergic and Apelinergic System Members in Acute Ischemic Stroke Patients

ler

Hakkoymaz

et al. 2020

Preprint

View full text Add to dashboard Cite

Objectives: To compare levels of catecholaminergic system members, renalase, cerebellin, and their subtrates, epinephrine, norepinephrine and dopamine and apelinergic system members, apelin, elabela and nitric oxide in the blood and urine of patients with acute ischemic stroke and healthy controls. Materials and Methods: 42 patients with acute ischemic stroke and 42 age and sex matched healthy controls were included. Patients had first ischemic stroke attack and aged older than 18 years old. Blood and urine samples were collected simultaneously and within first 24 hours after the onset of acute stroke clinical manifestations and were measured using enzyme-linked immunosorbent assay method. Results: The levels of serum and urine cerebellin, renalase, epinephrine, norperinephrine, dopamine, apelin, elebela and nitric oxide were similar in ischemic stroke and in control groups (P> 0.05). Strong correlations were found between renalase, cerebellin and catecholamine levels in serum and urine (p <0.001) both in stroke patients and controls. There were also strong correlations between apelin, elabela and NO levels in serum and urine (p <0.001) in two groups. Conclusions: Serum and urine cerebellin, renalase, epinephrine, norperinephrine, dopamine, apelin, elebela and nitric oxide levels do not significantly change in the acute phase of ischemic stroke. Strong correlations among renalase, cerebellin and catecholamines emphasize that these substances act together in healthy individuals and ischemic stroke patients. Similarly, strong correlations between apelin, elabela and NO indicate that these agents act together in healthy subjects and patients with ischemic stroke.

show abstract

“…Administration of renalase had also an intense and prolonged antihypertensive effect in an animal model of salt-sensitive hypertension 26 and renalase perfusion exerted heart-protective effects on a cardiac ischemia mouse model 19,27 . More recently, and independent of its enzymatic properties, renalase has been suggested to exert cytokine functions that provide cell protection by activating a receptor‐mediated pro-survival signaling cascade 28 . While reduced renalase plasma levels have been reported in studies using animal models of CKD 24,29 , the correlation in humans is less definite.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study suggests impact of chromosome 10 rs139401390 on kidney function in patients with coronary artery disease

Schmitz¹,

Kleber

Lenders

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is an independent risk factor for onset and progression of coronary artery disease (CAD). Discovery of predisposing loci for kidney function in CAD patients was performed using a genome-wide association approach. Inclusion criteria were CAD with ≥50% stenosis (≥1 coronary artery) and a creatinine-based estimated glomerular filtration rate (eGFR) of 30–75 ml/min/1.73 m 2 . An association of rs139401390 located to a region 58.8 kb upstream of renalase ( RNLS ) with eGFR was detected in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study (n = 499, p = 7.88 × 10 −9 , mean eGFR 60.7 ml/min/1.73 m 2 ). Direct genotyping of rs139401390A > G suggested increased eGFR by 12.0 ml/min/1.73 m 2 per A allele (p = 0.000004). Genome-wide replication of rs139401390A > G in the Coronary Artery Disease and Renal Failure (CAD-REF) registry with a mean eGFR of 47.8 ml/min/1.73 m 2 (n = 574, p = 0.033) was only nominally significant. Comparison of rs139401390 genotypes for risk of reduced kidney function in the overall LURIC study revealed higher adjusted odds ratios (OR) for eGFR <60 ml/min/1.73 m 2 for CAD patients (n = 1992, OR = 2.36, p = 0.008, G/A + G/G vs A/A) compared to patients with/without CAD (n = 2908, OR = 1.97, p = 0.014, G/A + G/G vs A/A). No significant risk elevation was detected in patients without CAD (n = 948, p = 0.571). rs139401390 may affect kidney function in CAD patients with mild reduction in eGFR.

show abstract

Extracellular renalase protects cells and organs by outside‐in signalling

Cited by 39 publications

References 40 publications

The serum protein renalase reduces injury in experimental pancreatitis

The serum protein renalase reduces injury in experimental pancreatitis

Levels of Serum and Urine Catecholaminergic and Apelinergic System Members in Acute Ischemic Stroke Patients

Genome-wide association study suggests impact of chromosome 10 rs139401390 on kidney function in patients with coronary artery disease

Contact Info

Product

Resources

About