Faculty Opinions recommendation of Heme oxygenase-1 inhibits renal tubular macroautophagy in acute kidney injury.

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.

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Heme oxygenase-1 induction mitigates burn-associated early acute kidney injury via the TLR4 signaling pathway

Burns ◽

10.1016/j.burns.2021.04.013 ◽

2021 ◽

Author(s):

Songxue Guo ◽

Meirong Yu ◽

Quan Fang ◽

Liping Zhang ◽

Chuangang You ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Heme Oxygenase ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Tlr4 Signaling ◽

Tlr4 Signaling Pathway

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The renoprotective effects of Heme Oxygenase-1 during contrast-induced acute kidney injury in preclinical diabetic models

Clinics ◽

10.6061/clinics/2021/e3002 ◽

2021 ◽

Vol 76 ◽

Author(s):

Cassiane Dezoti da Fonseca ◽

Mirian Watanabe ◽

Sheila Marques Fernandes Couto ◽

Alef Aragão Carneiro dos Santos ◽

Fernanda Teixeira Borges ◽

...

Keyword(s):

Acute Kidney Injury ◽

Heme Oxygenase ◽

Kidney Injury ◽

Heme Oxygenase 1

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6-Shogaol protects against ischemic acute kidney injury by modulating NF-κB and heme oxygenase-1 pathways

AJP Renal Physiology ◽

10.1152/ajprenal.00182.2019 ◽

2019 ◽

Vol 317 (3) ◽

pp. F743-F756 ◽

Cited By ~ 3

Author(s):

Sang Jun Han ◽

Mihwa Kim ◽

Vivette D. D’Agati ◽

H. Thomas Lee

Keyword(s):

Acute Kidney Injury ◽

Proximal Tubule ◽

Heme Oxygenase ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Zinc Protoporphyrin ◽

Mrna Synthesis ◽

Proximal Tubule Cells ◽

Tnf Α ◽

Tubule Cells

Acute kidney injury (AKI) due to renal ischemia-reperfusion (I/R) is a major clinical problem without effective therapy. Ginger is one of the most widely consumed spices in the world, and 6-shogaol, a major ginger metabolite, has anti-inflammatory effects in neuronal and epithelial cells. Here, we demonstrate our novel findings that 6-shogaol treatment protected against renal I/R injury with decreased plasma creatinine, blood urea nitrogen, and kidney neutrophil gelatinase-associated lipocalin mRNA synthesis compared with vehicle-treated mice subjected to renal I/R. Additionally, 6-shogaol treatment reduced kidney inflammation (decreased proinflammatory cytokine and chemokine synthesis as well as neutrophil infiltration) and apoptosis (decreased TUNEL-positive renal tubular cells) compared with vehicle-treated mice subjected to renal I/R. In cultured human and mouse kidney proximal tubule cells, 6-shogaol significantly attenuated TNF-α-induced inflammatory cytokine and chemokine mRNA synthesis. Mechanistically, 6-shogaol significantly attenuated TNF-α-induced NF-κB activation in human renal proximal tubule cells by reducing IKKαβ/IκBα phosphorylation. Furthermore, 6-shogaol induced a cytoprotective chaperone heme oxygenase (HO)-1 via p38 MAPK activation in vitro and in vivo. Consistent with these findings, pretreatment with the HO-1 inhibitor zinc protoporphyrin IX completely prevented 6-shogaol-mediated protection against ischemic AKI in mice. Taken together, our study showed that 6-shogaol protects against ischemic AKI by attenuating NF-κB activation and inducing HO-1 expression. 6-Shogaol may provide a potential therapy for ischemic AKI during the perioperative period.

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Heme Oxygenase-1 and Acute Kidney Injury following Cardiac Surgery

Cardiorenal Medicine ◽

10.1159/000357871 ◽

2014 ◽

Vol 4 (1) ◽

pp. 12-21 ◽

Cited By ~ 27

Author(s):

Frederic T. Billings ◽

Chang Yu ◽

John G. Byrne ◽

Michael R. Petracek ◽

Mias Pretorius

Keyword(s):

Acute Kidney Injury ◽

Cardiac Surgery ◽

Heme Oxygenase ◽

Kidney Injury ◽

Heme Oxygenase 1

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Hyperhomocysteinemia Accelerates Acute Kidney Injury to Chronic Kidney Disease Progression by Downregulating Heme Oxygenase-1 Expression

Antioxidants and Redox Signaling ◽

10.1089/ars.2017.7397 ◽

2019 ◽

Vol 30 (13) ◽

pp. 1635-1650 ◽

Cited By ~ 4

Author(s):

Shuang Li ◽

Bingbing Qiu ◽

Hong Lu ◽

Yunshi Lai ◽

Jixing Liu ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Disease Progression ◽

Heme Oxygenase ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Chronic Kidney Disease Progression ◽

Kidney Disease Progression

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Expression of ACE2 in the Intact and Acutely Injured Kidney

Kidney360 ◽

10.34067/kid.0001562021 ◽

2021 ◽

pp. 10.34067/KID.0001562021

Author(s):

Karl A. Nath ◽

Raman Deep Singh ◽

Joseph P. Grande ◽

Vesna D. Garovic ◽

Anthony J. Croatt ◽

...

Keyword(s):

Protein Expression ◽

Mrna Expression ◽

Heme Oxygenase ◽

Urinary Tract Obstruction ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Renal Tubular Epithelium ◽

Mrna And Protein Expression ◽

Intact Kidney ◽

Renal Tubular

Background. The actions of angiotensin-converting enzyme 2 (ACE2) oppose those of the renin-angiotensin-aldosterone system. Evidence supports ACE2 as a cytoprotectant in some tissues. This study examined ACE2 expression in models of acute kidney injury (AKI). Methods. ACE2 mRNA and protein expression, ACE2 activity, and ACE2 expression by immunofluorescence were assessed following ischemic AKI in mice. Renal ACE2 mRNA expression was evaluated in lipopolysaccharide-induced AKI in wildtype (C57BL/6J) mice, in heme oxygenase-1+/+ and heme oxygenase-1-/- mice, and following unilateral urinary tract obstruction (UUO) in wildtype mice. The effect of sex and age on renal ACE2 protein expression was also assessed. Results. In ischemic AKI, ACE2 mRNA and protein expression and ACE2 activity were reduced as compared with such indices in the intact kidney. In ischemic AKI, ACE2, which, in health, is prominently expressed in the renal tubular epithelium, especially in proximal tubules, exhibited decreased expression in these segments. Decreased ACE2 expression in AKI did not reflect reduced GFR per se as ACE2 mRNA expression was unaltered after UUO. Lipopolysaccharide induced renal ACE2 mRNA expression in wildtype mice, but this effect of lipopolysaccharide did not occur in heme oxygenase-1 deficient mice. In the intact kidney, renal ACE2 protein expression decreased in female mice as compared with male mice, but was unaltered with age. Conclusion. We conclude that renal ACE2 expression is decreased in ischemic AKI, one characterized by markedly reduced GFR and abundant cell death, but is upregulated in lipopolysaccharide-induced AKI; this latter effect requires heme oxygenase-1. Determining the significance of ACE2 expression in models of AKI merits further study. We also suggest that understanding the mechanism underlying ACE2 downregulation in AKI may offer insights relevant to COVID-19: ACE2 is downregulated after ACE2 mediates SARS-CoV-2 cellular entry; such downregulation promotes inflammation in COVID-19; and AKI commonly occurs and determines outcomes in COVID-19.

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