New insights into the role of heme oxygenase-1 in acute kidney injury

Nath, Meryl C.; Agarwal, Anupam

doi:10.23876/j.krcp.20.091

Cited by 30 publications

(29 citation statements)

References 97 publications

(136 reference statements)

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“…Spontaneous renal damage in both human and animal models invalidated for HMOX suggests that HO-1 is important for efficient renal function. The renal protective role of this enzyme has been confirmed in multiple models of renal challenge in HO-1 invalidation/inhibition or overexpression conditions [ 22 ]. However, the histological differences cited above illustrate the difficulties of transposing results from one species to another.…”

Section: About Heme Oxygenase-1 In Kidneymentioning

confidence: 99%

Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

Grünenwald

Roumenina

Frimat

2021

IJMS

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The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.

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Section: About Heme Oxygenase-1 In Kidneymentioning

confidence: 99%

Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

Grünenwald

Roumenina

Frimat

2021

IJMS

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“…HO-1 expression has been associated with tissue protection in models of acute kidney injury (AKI) induced by sepsis and other insults such ischemia/reperfusion (I/R) and exposure to cisplatin [ 35 , 201 ]. Early studies recognized the potential of heme both as a mediator of kidney injury and as a means for therapeutic preconditioning to induce HO-1 [ 202 ].…”

Section: Role Of Heme Oxygenase In Mediating Acute Inflammationmentioning

confidence: 99%

“…Importantly, circulating heme released from hemoglobin during hemolytic disorders, can injure vascular endothelium, leading to compromised vascular function [ 19 , 20 , 21 , 22 ]. In human diseases, free heme has been implicated as a harmful mediator in sickle cell disease (SCD) [ 23 , 24 , 25 , 26 , 27 ], malaria [ 14 , 28 , 29 ], sepsis [ 30 ], acute lung injury (ALI) [ 31 , 32 ] acute kidney injury (AKI) [ 33 , 34 , 35 ], and other inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders

Ryter¹

2021

IJMS

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The heme molecule serves as an essential prosthetic group for oxygen transport and storage proteins, as well for cellular metabolic enzyme activities, including those involved in mitochondrial respiration, xenobiotic metabolism, and antioxidant responses. Dysfunction in both heme synthesis and degradation pathways can promote human disease. Heme is a pro-oxidant via iron catalysis that can induce cytotoxicity and injury to the vascular endothelium. Additionally, heme can modulate inflammatory and immune system functions. Thus, the synthesis, utilization and turnover of heme are by necessity tightly regulated. The microsomal heme oxygenase (HO) system degrades heme to carbon monoxide (CO), iron, and biliverdin-IXα, that latter which is converted to bilirubin-IXα by biliverdin reductase. Heme degradation by heme oxygenase-1 (HO-1) is linked to cytoprotection via heme removal, as well as by activity-dependent end-product generation (i.e., bile pigments and CO), and other potential mechanisms. Therapeutic strategies targeting the heme/HO-1 pathway, including therapeutic modulation of heme levels, elevation (or inhibition) of HO-1 protein and activity, and application of CO donor compounds or gas show potential in inflammatory conditions including sepsis and pulmonary diseases.

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“…Acute kidney injury (AKI), characterized by a rapid increase in serum creatinine and/or a decrease in urine output, is associated with high rates of morbidity and mortality in hospital and outpatient settings ( 56 , 57 ). Despite the heterogeneity of causes, the response following an acute insult involves similar pathways, including apoptosis, necrosis, and infiltration of inflammatory cells ( 58 ).…”

Section: Acute Kidney Injurymentioning

confidence: 99%

“…The preventive role of HO-1, as well as the induction of other cytoprotective stress proteins, is collectively referred in the literature as “preconditioning treatment” ( 56 ). Numerous subsequent studies have confirmed the potential of pharmacologic or genetic HO-1 induction in immune modulation against AKI ( 71 , 82 , 83 ).…”

Section: Acute Kidney Injurymentioning

confidence: 99%

Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease

Han

et al. 2021

Front. Med.

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Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, has attracted widespread attention in recent years due to its cytoprotective properties. As an enzyme with known anti-oxidative functions, HO-1 plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. Many strategies, such as the administration of HO-1-overexpressing macrophages, use of phytochemicals, and carbon monoxide-based therapies, have been developed to target HO-1 in a variety of nephropathological animal models, indicating that HO-1 is a promising protein for the treatment of kidney diseases. Here, we briefly review the effects of HO-1 induction on specific immune cell populations with the aim of exploring the potential therapeutic roles of HO-1 and designing HO-1-based therapeutic strategies for the treatment of kidney diseases.

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New insights into the role of heme oxygenase-1 in acute kidney injury

Cited by 30 publications

References 97 publications

Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

Significance of Heme and Heme Degradation in the Pathogenesis of Acute Lung and Inflammatory Disorders

Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease

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