The impact of hypoxia-inducible factors in the pathogenesis of kidney diseases: a link through cell metabolism

Foresto-Neto, Orestes; Silva, Ana Ruth Paolinetti Alves da; Cipelli, Marcella; Santana-Novelli, Fernanda Paula Roncon; Câmara, Niels Olsen Saraiva

doi:10.23876/j.krcp.23.012

Cited by 3 publications

(1 citation statement)

References 176 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that the downstream targets of HIF-1 include genes involved in iron regulation, glycolysis, cell survival, erythropoiesis, and angiogenesis [98]. Under typical conditions, the regulation of HIF-1 involves its α subunit being targeted for ubiquitination by the von Hippel-Lindau protein E3 ubiquitin ligase, due to the action of prolyl hydroxylase (PHD) [99]. This usually results in its degradation.…”

Section: Hif-1 Activation In Hypoxia: a Double-edged Swordmentioning

confidence: 99%

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia

Chae,

Kim,

Park

2023

Antioxidants

View full text Add to dashboard Cite

Oxidative stress, a hallmark pathophysiological feature in diabetic kidney disease (DKD), arises from the intricate interplay between pro-oxidants and anti-oxidants. While hyperglycemia has been well established as a key contributor, lipotoxicity emerges as a significant instigator of oxidative stress. Lipotoxicity encompasses the accumulation of lipid intermediates, culminating in cellular dysfunction and cell death. However, the mechanisms underlying lipotoxic kidney injury in DKD still require further investigation. The key role of cell metabolism in the maintenance of cell viability and integrity in the kidney is of paramount importance to maintain proper renal function. Recently, dysfunction in energy metabolism, resulting from an imbalance in oxygen levels in the diabetic condition, may be the primary pathophysiologic pathway driving DKD. Therefore, we aim to shed light on the pivotal role of oxidative stress related to lipotoxicity and renal hypoxia in the initiation and progression of DKD. Multifaceted mechanisms underlying lipotoxicity, including oxidative stress with mitochondrial dysfunction, endoplasmic reticulum stress activated by the unfolded protein response pathway, pro-inflammation, and impaired autophagy, are delineated here. Also, we explore potential therapeutic interventions for DKD, targeting lipotoxicity- and hypoxia-induced oxidative stress. These interventions focus on ameliorating the molecular pathways of lipid accumulation within the kidney and enhancing renal metabolism in the face of lipid overload or ameliorating subsequent oxidative stress. This review highlights the significance of lipotoxicity, renal hypoxia-induced oxidative stress, and its potential for therapeutic intervention in DKD.

show abstract

Section: Hif-1 Activation In Hypoxia: a Double-edged Swordmentioning

confidence: 99%

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia

Chae,

Kim,

Park

2023

Antioxidants

View full text Add to dashboard Cite

show abstract

Effect of therapeutic erythrocytapheresis on outcomes and renal benefit in patients with high-altitude polycythemia: a real-world study

Ouyang,

Zhang,

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Kidney injury from high-altitude polycythemia (HAPC) is common, yet few studies have explored effective treatments. This research assessed the renal benefits of therapeutic erythrocytapheresis (TE) in HAPC patients, analyzing the efficacy of single versus multiple treatments. From 2017 to 2023, 631 patients undergoing TE were included. Findings showed notable improvements in hemoglobin levels (median: 228.00 vs. 169.00 g/L, p < 0.001), estimated glomerular filtration rate (eGFR) (median: 100.24 vs. 105.92 ml/min/1.73 m 2 , p < 0.001), and uric acid levels (median 495.00 vs. 405.00 µmol/L, p < 0.001). The rate of patients with negative urine protein tests rose from 54.58 to 92.83%. Analysis indicated that a lower pre-treatment eGFR was associated with significant renal improvement post-treatment (OR 0.959, 95% CI 0.945–0.972, p < 0.001), even when adjusting for hemoglobin and other factors (OR 0.962, 95% CI 0.947–0.977, p < 0.001). After propensity score matching, 168 patients were categorized based on the number of treatments. Compared to single treatment, multiple treatments resulted in significantly lower hemoglobin levels post-treatment (median: 177.00 vs. 165.00 g/L, p < 0.001). TE proves to be a beneficial treatment for HAPC, improving hemoglobin and renal function. Multiple treatments may be preferable for maintaining stable hemoglobin levels. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-80609-6.

show abstract

Hypoxia Modulates Sodium Chloride Co-transporter via CaMKII-β Pathway: An In Vitro Study with mDCT15 Cells

Liang,

Ueda,

Ogura

et al. 2024

Life

View full text Add to dashboard Cite

Background: Hypoxia plays a crucial role in regulating various cellular functions, including ion-transport mechanisms in the kidney. The sodium-chloride co-transporter (NCC) is essential for sodium reabsorption in the distal convoluted tubule (DCT). However, the effects of hypoxia on NCC expression and its regulatory pathways remain unclear. We aimed to explore the effects and potential mechanisms of hypoxia on NCC in vitro. Methods: mDCT15 cells were treated with cobalt chloride (CoCl2) at a concentration of 300 μmol/L to induce hypoxia. The cells were harvested at different time points, namely 30 min, 1 h, 6 h, and 24 h, and the expression of NCC and CaMKII-β was analyzed using Western blot. Results: A time-dependent upregulation of NCC and CaMKII-β expression in response to CoCl2-induced hypoxia. KN93 reversed the effect of CoCl2 on NCC and phosphorylated NCC expression. Conclusions: Hypoxia, mediated through cobalt chloride treatment, upregulates NCC expression via the CaMKII-β pathway in mDCT15 cells.

show abstract

The impact of hypoxia-inducible factors in the pathogenesis of kidney diseases: a link through cell metabolism

Cited by 3 publications

References 176 publications

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia

Effect of therapeutic erythrocytapheresis on outcomes and renal benefit in patients with high-altitude polycythemia: a real-world study

Hypoxia Modulates Sodium Chloride Co-transporter via CaMKII-β Pathway: An In Vitro Study with mDCT15 Cells

Contact Info

Product

Resources

About