Heme-Oxygenase and Kidney Transplantation: A Potential for Target Therapy?

Mou

et al. 2022

Front. Mol. Biosci.

Renal fibrosis is a common feature of chronic kidney disease (CKD), and can lead to the destruction of normal renal structure and loss of kidney function. Little progress has been made in reversing fibrosis in recent years. Ferroptosis is more immunogenic than apoptosis due to the release and activation of damage-related molecular patterns (DAMPs) signals. In this paper, the relationship between renal fibrosis and ferroptosis was reviewed from the perspective of iron metabolism and lipid peroxidation, and some pharmaceuticals or chemicals associated with both ferroptosis and renal fibrosis were summarized. Other programmed cell death and ferroptosis in renal fibrosis were also firstly reviewed for comparison and further investigation.

Section: Ferroptosis In Chronic Renal Injury and Fibrosismentioning

confidence: 99%

Therapeutic Implications of Ferroptosis in Renal Fibrosis

Mou

et al. 2022

Front. Mol. Biosci.

“…Indeed, long (45 min) but not short (15 min) warm ischemia induced inflammation, local tissue injury, higher cell-free heme concentrations and increases in HO-1 but also C5aR, IL-6 and TNF-α expression [ 103 ]. If cold ischemia time is also associated with delayed graft function, HO-1 expression during this period is probably a bystander effect of the preceding warm ischemia time, though its role has been poorly studied [ 250 ]. Interestingly, HO-1 also plays a determining role in transplantation, besides this major protective role in I/R, by preventing Rapamycine toxicity [ 221 ], acute rejection (affecting the recipient cellular response and by protecting the graft itself) [ 251 , 252 ] and improving long-term graft survival [ 256 ].…”

Section: Ho-1 In Kidney Diseasesmentioning

confidence: 99%

Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

Grünenwald

Roumenina

Frimat

2021

IJMS

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.

“…The prolonged duration of warm ischemia results in inflammation, local tissue injury, higher free heme levels, and upregulated levels of HO-1, C5a receptor (C5aR), IL-6, and TNF-α (200). However, during the cold ischemia period, high HO-1 expression is related to an inferior outcome, although previous studies cannot identify a direct association between the longer ischemia time and the higher HO-1 expression (201). In a rat model of kidney transplantation, hyperthermic preconditioning or Co-PP induces HO-1 expression.…”

Section: Kidney Transplantationmentioning

confidence: 99%

Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease

Han

et al. 2021

Front. Med.

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.