scholarly journals P2X7 receptor inhibition protects against ischemic acute kidney injury in mice

2015 ◽  
Vol 308 (6) ◽  
pp. C463-C472 ◽  
Author(s):  
Yanli Yan ◽  
Jianwen Bai ◽  
Xiaoxu Zhou ◽  
Jinhua Tang ◽  
Chunming Jiang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
P2x7 Receptor ◽  
Renal Tubule ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Protective Effects ◽  
Proinflammatory Response ◽  
Hypertensive Nephropathy

Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the development of experimental nephritis and diabetic and hypertensive nephropathy. However, its role in acute kidney injury (AKI) remains unknown. In this study, we examined the effects of P2X7R inhibition in a murine model of ischemia-reperfusion (I/R)-induced AKI using A438079, a selective inhibitor of P2X7R. At 24 h after I/R, mice developed renal dysfunction and renal tubular damage, which was accompanied by elevated expression of P2X7R. Early administration of A438079 immediately or 6 h after the onset of reperfusion protected against renal dysfunction and attenuated kidney damage whereas delayed administration of A438079 at 24 h after restoration of perfusion had no protective effects. The protective actions of A438079 were associated with inhibition of renal tubule injury and cell death and suppression of renal expression of monocyte chemotactic protein-1 and regulated upon expression normal T cell expressed and secreted (RANTES). Moreover, I/R injury led to an increase in phosphorylation (activation) of extracellular signal-regulated kinases 1/2 in the kidney; treatment with A438079 diminished this response. Collectively, these results indicate that early P2X7R inhibition is effective against renal tubule injury and proinflammatory response after I/R injury and suggest that targeting P2X7R may be a promising therapeutic strategy for treatment of AKI.

scholarly journals Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury

Biology Open ◽  
2021 ◽  
Author(s):  
Taro Miyagawa ◽  
Yasunori Iwata ◽  
Megumi Oshima ◽  
Hisayuki Ogura ◽  
Koichi Sato ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Advanced Glycation End Products ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Advanced Glycation ◽  
Renal Tubular Damage ◽  
Glycation End Products ◽  
End Products ◽  
Renal Tubular

The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE (esRAGE), a splice variant, are soluble isoforms (sRAGE) that act as organ-protective decoys. However, the pathophysiologic roles of RAGE/sRAGE in acute kidney injury (AKI) remain unclear. We found that AKI was more severe, with enhanced renal tubular damage, macrophage infiltration, and fibrosis, in mice lacking both RAGE and sRAGE than in wild-type control mice. Using murine tubular epithelial cells (TECs), we demonstrated that hypoxia upregulated messenger RNA (mRNA) expression of HMGB1 and tumor necrosis factor α (TNF-α), whereas RAGE and esRAGE expressions were paradoxically decreased. Moreover, the addition of recombinant sRAGE canceled hypoxia-induced inflammation and promoted cell viability in cultured TECs. sRAGE administration prevented renal tubular damage in models of ischemia/reperfusion-induced AKI and of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. These results suggest that sRAGE is a novel therapeutic option for AKI.

scholarly journals Genetic Deletion of Vasohibin-2 Exacerbates Ischemia-Reperfusion-Induced Acute Kidney Injury

2020 ◽  
Vol 21 (12) ◽  
pp. 4545 ◽  
Author(s):  
Hiromasa Miyake ◽  
Katsuyuki Tanabe ◽  
Satoshi Tanimura ◽  
Yuri Nakashima ◽  
Tomoyo Morioka ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Neutrophil Infiltration ◽  
Endothelial Damage ◽  
Tubular Damage ◽  
Renal Tubules ◽  
Inflammatory Infiltration ◽  
Peritubular Capillaries

Acute kidney injury (AKI) has been increasingly recognized as a risk factor for transition to chronic kidney disease. Recent evidence suggests that endothelial damage in peritubular capillaries can accelerate the progression of renal injury. Vasohibin-2 (VASH2) is a novel proangiogenic factor that promotes tumor angiogenesis. However, the pathophysiological roles of VASH2 in kidney diseases remain unknown. In the present study, we examined the effects of VASH2 deficiency on the progression of ischemia–reperfusion (I/R) injury-induced AKI. I/R injury was induced by bilaterally clamping renal pedicles for 25 min in male wild-type (WT) and Vash2 homozygous knockout mice. Twenty-four hours later, I/R injury-induced renal dysfunction and tubular damage were more severe in VASH2-deficient mice than in WT mice, with more prominent neutrophil infiltration and peritubular capillary loss. After induction of I/R injury, VASH2 expression was markedly increased in injured renal tubules. These results suggest that VASH2 expression in renal tubular epithelial cells might be essential for alleviating I/R injury-induced AKI, probably through protecting peritubular capillaries and preventing inflammatory infiltration.

17β-Estradiol Accelerated Renal Tubule Regeneration in Male Rats After Ischemia/Reperfusion-Induced Acute Kidney Injury

Shock ◽  
2016 ◽  
Vol 46 (2) ◽  
pp. 158-163 ◽  
Author(s):  
Chia-Chun Wu ◽  
Chia-Yu Chang ◽  
Sheng-Tsung Chang ◽  
Sheng-Hsien Chen
Keyword(s):  
Acute Kidney Injury ◽  
Renal Tubule ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Male Rats ◽  
17Β Estradiol

scholarly journals FGF23 ameliorates ischemia-reperfusion induced acute kidney injury via modulation of endothelial progenitor cells: targeting SDF-1/CXCR4 signaling

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Huang-Ming Chang ◽  
Kang-Yung Peng ◽  
Chieh-Kai Chan ◽  
Chiao-Yin Sun ◽  
Ying-Ying Chen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Fibroblast Growth Factor 23 ◽  
Kidney Injury ◽  
In Vitro Assays ◽  
Tubular Damage ◽  
Endothelial Progenitor ◽  
Cxcr4 Signaling

AbstractThe levels of fibroblast growth factor 23 (FGF23) rapidly increases after acute kidney injury (AKI). However, the role of FGF23 in AKI is still unclear. Here, we observe that pretreatment with FGF23 protein into ischemia-reperfusion induced AKI mice ameliorates kidney injury by promoting renal tubular regeneration, proliferation, vascular repair, and attenuating tubular damage. In vitro assays demonstrate that SDF-1 induces upregulation of its receptor CXCR4 in endothelial progenitor cells (EPCs) via a non-canonical NF-κB signaling pathway. FGF23 crosstalks with the SDF-1/CXCR4 signaling and abrogates SDF-1-induced EPC senescence and migration, but not angiogenesis, in a Klotho-independent manner. The downregulated pro-angiogenic IL-6, IL-8, and VEGF-A expressions after SDF-1 infusion are rescued after adding FGF23. Diminished therapeutic ability of SDF-1-treated EPCs is counteracted by FGF23 in a SCID mouse in vivo AKI model. Together, these data highlight a revolutionary and important role that FGF23 plays in the nephroprotection of IR-AKI.

scholarly journals Protective effects of D-005, a lipid extract from Acrocomia crispa fruits, against ischemia/reperfusion-induced acute kidney injury in rats

2019 ◽  
Vol 38 (4) ◽  
pp. 462-471
Author(s):  
Ambar Oyarzábal-Yera ◽  
Sandra Rodríguez-Salgueiro ◽  
Nelson Merino-García ◽  
Leyanis Ocaña-Nápoles ◽  
Lucía González-Núñez ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Lipid Extract ◽  
Protective Effects

scholarly journals Protective Effects of Bee Venom against Endotoxemia-Related Acute Kidney Injury in Mice

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 154 ◽  
Author(s):  
Jung-Yeon Kim ◽  
Sun-Jae Lee ◽  
Young-In Maeng ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
Cell Apoptosis ◽  
Immune Cell ◽  
Medical Condition ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Bee Venom ◽  
Protective Effects ◽  
Structural Injury

Sepsis-associated acute kidney injury (AKI) is a leading cause of death in hospitalized patients worldwide. Despite decades of effort, there is no effective treatment for preventing the serious medical condition. Bee venom has long been used to treat a variety of inflammatory diseases. However, whether bee venom has protective effects against lipopolysaccharide (LPS)-induced AKI has not been explored. The aim of this study was to evaluate the effects of bee venom on LPS-induced AKI. The administration of bee venom alleviated renal dysfunction and structural injury in LPS-treated mice. Increased renal levels of tubular injury markers after LPS treatment were also suppressed by bee venom. Mechanistically, bee venom significantly reduced plasma and tissue levels of inflammatory cytokines and immune cell infiltration into damaged kidneys. In addition, mice treated with bee venom exhibited reduced renal expression of lipid peroxidation markers after LPS injection. Moreover, bee venom attenuated tubular cell apoptosis in the kidneys of LPS-treated mice. In conclusion, these results suggest that bee venom attenuates LPS-induced renal dysfunction and structural injury via the suppression of inflammation, oxidative stress, and tubular cell apoptosis, and might be a useful therapeutic option for preventing endotoxemia-related AKI.

scholarly journals Preventive Effects of a Natural Anti-Inflammatory Agent, Astragaloside IV, on Ischemic Acute Kidney Injury in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Shufeng Tan ◽  
Guofu Wang ◽  
Yongping Guo ◽  
Dingkun Gui ◽  
Niansong Wang
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Astragaloside Iv ◽  
Inflammatory Agent ◽  
Genes Expression ◽  
Bilateral Renal Artery ◽  
Anti Inflammatory ◽  
Preventive Effects

This study investigated the anti-inflammatory effects of astragaloside IV(AS-IV) on ischemia/reperfusion (IR) induced acute kidney injury (AKI) in rats. Experimental model of ischemic AKI was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 12 h and 24 h, respectively. AS-IV was orally administered once a day to rats at 10 and 20 mg·kg−1·d−1for 7 days prior to ischemia. AS-IV pretreatment significantly decreased serum urea, creatinine, and cystatin C levels at 12 h and 24 h of reperfusion in AKI rats. AS-IV pretreatment also ameliorated tubular damage and suppressed the phosphorylation of p65 subunit of NF-κB in AKI rats. Moreover, NF-κB and MPO activity as well as serum and tissue levels of TNF-α, MCP-1, and ICAM-1 were elevated in AKI rats. All of these abnormalities were prevented by AS-IV. Furthermore, AS-IV downregulated the mRNA expression of NF-κB, TNF-α, MCP-1, and ICAM-1 in AKI rats. These results suggest that AS-IV might be developed as a novel therapeutic approach to prevent ischemic AKI through inhibition of NF-κB mediated inflammatory genes expression.

1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose from Galla rhois Ameliorates Renal Tubular Injury and Microvascular Inflammation in Acute Kidney Injury Rats

2018 ◽  
Vol 46 (04) ◽  
pp. 785-800 ◽  
Author(s):  
Ji Hun Park ◽  
Min Chol Kho ◽  
Hyun Cheol Oh ◽  
Youn Chul Kim ◽  
Jung Joo Yoon ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Urine Volume ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Tubular Dysfunction ◽  
Tubular Injury ◽  
Microvascular Inflammation ◽  
Renal Tubular

Renal ischemia-reperfusion injury (IRI), an important cause of acute kidney injury (AKI), causes increased renal tubular injury and microvascular inflammation. 1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-penta-O-galloyl-[Formula: see text]-D-glucose (PGG) from Galla rhois has anticancer, anti-oxidation and angiogenesis effects. We examined protective effects of PGG on IRI-induced acute AKI. Clamping both renal arteries for 45[Formula: see text]min induced isechemia and then reperfusion. Treatment with PGG (10[Formula: see text]mg/kg/day and 50[Formula: see text]mg/kg/day for four days) significantly ameliorated urine volume, urine osmolality, creatinine clearance (Ccr) and blood urea nitrogen (BUN). In addition, PGG increased aquaporine 1/2/3, Na[Formula: see text]-K[Formula: see text]-ATPase and urea transporter (UT-B) and decreased ICAM-1, MCP-1, and HMGB-1 expression. In this histopathologic study, PGG improved glomerular and tubular damage. Immunohistochemistry results showed that PGG increased aquaporine 1/2, and Na[Formula: see text]-K[Formula: see text] ATPase and decreased ICAM-1 expression. These findings suggest that PGG ameliorates tubular injury including tubular dysfunction and microvascular inflammation in IRI-induced AKI rats.

scholarly journals NLRP3 associated with chronic kidney disease progression after ischemia/reperfusion-induced acute kidney injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Zhihuang Zheng ◽  
Kexin Xu ◽  
Chuanlei Li ◽  
Chenyang Qi ◽  
Yili Fang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Immune Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Chronic Phase ◽  
Kidney Injury ◽  
Receptor Protein ◽  
Tubular Damage

AbstractNod-like receptor protein 3 (NLRP3), as an inflammatory regulator, has been implicated in acute kidney injury (AKI). Failed recovery after AKI can lead to chronic kidney disease (CKD). However, the role of NLRP3 in the AKI-CKD transition is still unknown. A mild or severe AKI mouse model was performed by using ischemia-reperfusion injury (IRI). We evaluated the renal NLRP3 expression in acute and chronic phases of ischemic AKI, respectively. Although serum creatinine (Cr) and blood urea nitrogen (BUN) levels in AKI chronic phase were equivalent to normal baseline, histological analysis and fibrotic markers revealed that severe AKI-induced maladaptive tubular repair with immune cell infiltration and fibrosis. Tubular damage was restored completely in mild AKI rather than in severe AKI. Of note, persistent overexpression of NLRP3 was also found in severe AKI but not in mild AKI. In the severe AKI-induced chronic phase, there was a long-term high level of NLRP3 in serum or urine. Overt NLRP3 was mainly distributed in the abnormal tubules surrounded by inflammatory infiltrates and fibrosis, which indicated the maladaptive repair. Renal Nlrp3 overexpression was correlated with infiltrating macrophages and fibrosis. Renal NLRP3 signaling-associated genes were upregulated after severe AKI by RNA-sequencing. Furthermore, NLRP3 was found increased in renal tubular epitheliums from CKD biopsies. Together, persistent NLRP3 overexpression was associated with chronic pathological changes following AKI, which might be a new biomarker for evaluating the possibility of AKI-CKD transition.

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