Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment

Madjène, Lydia Celia; Danelli, Luca; Dahdah, Albert; Vibhushan, Shamila; Bex-Coudrat, Julie; Pacreau, Emeline; Vaugier, Céline; Claver, Julien; Rolas, Loïc; Pons, Maguelonne; Madera-Salcedo, Iris K.; Beghdadi, Walid; El-Ghoneimi, Alaa; Benhamou, Marc; Launay, Pierre; Åbrink, Magnus; Pejler, Gunnar; Moura, Ivan C.; Charles, Nicolas; Daugas, Éric; Périanin, Axel; Blank, Ulrich

doi:10.1016/j.kint.2019.08.037

Cited by 20 publications

(19 citation statements)

References 85 publications

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“…Evidence-Based Complementary and Alternative Medicine mediator damage [17][18][19]. Consistent with the above findings, we noted that the Na + -K + -ATPase and Ca 2+ -ATPase activities decreased after CPR but increased after SFI treatment.…”

supporting

confidence: 88%

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation

Tang

Cui

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. To comprehensively evaluate the protective effect of Shenfu injection (SFI) on renal ischaemia/reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) through neutrophil gelatinase-associated lipocalin (NGAL) and to explore effective monitoring of early renal injuries after CPR. Methods. Thirty healthy minipigs were randomly divided into 3 groups: sham operation (SO) (n = 6), control (n = 12), and SFI (n = 12). The SO group underwent only catheterization, whereas the control and SFI groups were subjected to program-controlled electrical stimulation to establish a cardiac arrest (CA) model due to ventricular fibrillation. After CPR, the return of spontaneous circulation was achieved. Each animal in the SFI group was intravenously injected with SFI after resuscitation. Haemodynamic parameters were monitored at baseline and 2, 6, 12, and 24 hr after CPR. At each time point, venous blood samples were collected for NGAL, creatinine, and ATPase screening. Results. After CA, the MAP, CPP, and CO of the animals in the control and SFI groups decreased significantly. However, at 6 hr after CPR, the MAP, CPP, and CO of the animals in the SFI group began to recover gradually; the differences between the control and SFI groups were significant (P<0.005). The renal damage immediately after CPR appeared to be significant in the pathological examinations. However, the degree of renal injury in the SFI group improved significantly, and the apoptosis index was also notably reduced. The blood and urine NGAL levels were clearly elevated after CPR. The greatest increase in NGAL was found in the control group, which was significantly different from that of the SFI group (P<0.001). SFI can significantly increase the ATPase activity of kidney tissues after CPR and improve abnormal caspase-3 protein expression. Conclusion. SFI can effectively prevent acute kidney injuries caused by CPR through improving energy metabolism and inhibiting apoptosis.

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supporting

confidence: 88%

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation

Tang

Cui

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…The enzyme chymase, present in mast cells, has been reported to be a potent antiin ammatory factor in renal injury by limiting neutrophil hyperactivation, recruitment, and associated damage. 22 To further investigate the function of CFAP45 in DKD, 349 CFAP45-associated DEGs were subjected to GO and KEGG pathway enrichment analysis. Analysis indicated that mitochondrial metabolic dysfunction may play an important role in the development of DKD because glucose (glycolysis/gluconeogenesis, amino sugar, and nucleotide sugar metabolism), fatty acids (phospholipid transporter activity, intramembrane lipid transporter activity, and fatty acid metabolism), amino acids (ubiquitin-dependent protein catabolic processes, valine, leucine, and isoleucine degradation), and other metabolic substrates (e.g., the TCA cycle) all represent chemical fuels that are used by the mitochondria to make ATP (oxidoreductase activity acting on NADH).…”

Section: Discussionmentioning

confidence: 99%

CFAP45 is a Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease

Chen¹,

Shen²,

Shi³

et al. 2021

Preprint

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Background: Cilia and Flagella Associated Protein 45 (CFAP45) is known to be involved in the regulation of ciliary motility. However, its potential role in diabetic kidney disease (DKD) remains unknown. This study demonstrated the role of CFAP45 in the development of DKD based on the Gene Expression Omnibus database.Methods: First, we investigated the expression of CFAP45 in a whole-genome expression microarray (GSE30122). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as Gene Set Enrichment Analysis (GSEA), were then conducted to identify the key signaling pathways associated with CFAP45. The networks between transcript factors and hub genes were then constructed by Cytoscape software.Findings: The expression levels of CFAP45 mRNA were reduced in DKD samples as compared to normal samples. Receiver operating characteristic (ROC) curve analysis suggested the significant discriminatory power (area under curve [AUC] = 0.811) of CFAP45 between DKD and normal tissues. Low expression levels of CFAP45 were correlated with apoptosis, senescence and the induction of mast cell infiltration. Function enrichment analysis indicated that CFAP45 is involved in the most significant hallmarks of mitochondrial metabolism dysfunction, including glycolysis and gluconeogenesis, fatty acid metabolism and degradation, ubiquitin-dependent protein catabolic processes, the tricarboxylic acid cycle (TCA) cycle, the action of oxidoreductase on Nicotinamide adenine dinucleotide (NADH), and the peroxisome proliferator-activated receptor (PPAR) signaling pathways located in the mitochondrial matrix and the lysosomal membrane. The transcription factor SMAD4 was found to negatively regulate the PPAR γ coactivator 1α (PGC1α). Interpretation: CFAP45 may regulate mitochondrial metabolic activity by affecting the function of the primary cilium on the kidney epithelial cells. CFAP45 may serve as a potential biomarker for the diagnosis and treatment of DKD.

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“…However, it was reasoned that these differences could be explained by the specific pathophysiological phenotypes associated with the respective types of lesions, and possibly related to different disease kinetics of the models [125]. A protective function for chymase has also been seen in ischemic kidney injury, where Mcpt4 was shown to limit neutrophil recruitment and activation [126]. It was suggested that chymase exerted this role by modifying the surface expression of CD11b integrin and P/E-selectin [126].…”

Section: Chymase In Inflammatory Kidney Diseasementioning

confidence: 99%

“…A protective function for chymase has also been seen in ischemic kidney injury, where Mcpt4 was shown to limit neutrophil recruitment and activation [126]. It was suggested that chymase exerted this role by modifying the surface expression of CD11b integrin and P/E-selectin [126].…”

Section: Chymase In Inflammatory Kidney Diseasementioning

confidence: 99%

Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors

Pejler

2020

J Innate Immun

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Mast cells are now recognized as key players in diverse pathologies, but the mechanisms by which they contribute in such settings are only partially understood. Mast cells are packed with secretory granules, and when they undergo degranulation in response to activation the contents of the granules are expelled to the extracellular milieu. Chymases, neutral serine proteases, are the major constituents of the mast cell granules and are hence released in large amounts upon mast cell activation. Following their release, chymases can cleave one or several of a myriad of potential substrates, and the cleavage of many of these could potentially have a profound impact on the respective pathology. Indeed, chymases have recently been implicated in several pathological contexts, in particular through studies using chymase inhibitors and by the use of chymase-deficient animals. In many cases, chymase has been shown to account for mast cell-dependent detrimental effects in the respective conditions and is therefore emerging as a promising drug target. On the other hand, chymase has been shown to have protective roles in other pathological settings. More unexpectedly, chymase has also been shown to control certain homeostatic processes. Here, these findings are reviewed.

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Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment

Cited by 20 publications

References 85 publications

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation

CFAP45 is a Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease

Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors

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Mast cell chymase protects against acute ischemic kidney injury by limiting neutrophil hyperactivation and recruitment

Cited by 20 publications

References 85 publications

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation

Effect of Shenfu Injection on Porcine Renal Function after Cardiopulmonary Resuscitation

CFAP45 is a&nbsp;Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease

Novel Insight into the in vivo Function of Mast Cell Chymase: Lessons from Knockouts and Inhibitors

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CFAP45 is a Potential Predictor of Mitochondrial Dysfunction in Diabetic Kidney Disease