Promising novel therapeutic targets for kidney disease: Emphasis on kidney-specific proteins

Sen, Tathambika Tejeswini; Kale, Ajinath; Lech, Maciej; Anders, Hans‐Joachim; Malek, Vajir

doi:10.1016/j.drudis.2022.103466

Cited by 5 publications

(1 citation statement)

References 89 publications

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“…CKD characterized by declined kidney function leads to an accumulation of waste products, including uremic toxins, in the bloodstream and tissues, which can contribute to the progression of the disease and further deterioration to kidney failure [4]. The burden of CKD is expected to continue to increase in the coming years, highlighting the need for effective prevention and management strategies to reduce its impact on public health [5,6].…”

Section: Introductionmentioning

confidence: 99%

Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence

Ribeiro

Liu

Srebrzynski

et al. 2023

IJMS

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In this study, we investigated the impact of the uremic toxin indoxyl sulfate on macrophages and tubular epithelial cells and its role in modulating the response to lipopolysaccharide (LPS). Indoxyl sulfate accumulates in the blood of patients with chronic kidney disease (CKD) and is a predictor of overall and cardiovascular morbidity/mortality. To simulate the uremic condition, primary macrophages and tubular epithelial cells were incubated with indoxyl sulfate at low concentrations as well as concentrations found in uremic patients, both alone and upon LPS challenge. The results showed that indoxyl sulfate alone induced the release of reactive oxygen species and low-grade inflammation in macrophages. Moreover, combined with LPS (proinflammatory conditions), indoxyl sulfate significantly increased TNF-α, CCL2, and IL-10 release but did not significantly affect the polarization of macrophages. Pre-treatment with indoxyl sulfate following LPS challenge induced the expression of aryl hydrocarbon receptor (Ahr) and NADPH oxidase 4 (Nox4) which generate reactive oxygen species (ROS). Further, experiments with tubular epithelial cells revealed that indoxyl sulfate might induce senescence in parenchymal cells and therefore participate in the progression of inflammaging. In conclusion, this study provides evidence that indoxyl sulfate provokes low-grade inflammation, modulates macrophage function, and enhances the inflammatory response associated with LPS. Finally, indoxyl sulfate signaling contributes to the senescence of tubular epithelial cells during injury.

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Section: Introductionmentioning

confidence: 99%

Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence

Ribeiro

Liu

Srebrzynski

et al. 2023

IJMS

Self Cite

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Oxidative stress and NRF2 signaling in kidney injury

Ng,

Kim,

Yanti

et al. 2024

Toxicol Res.

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Diagnostic, prognostic and therapeutic aspects of apelin in cardiovascular diseases

Alieva,

Teplova,

Reznik

et al. 2024

Russian Medicine

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Biological markers have been thoroughly incorporated into clinical practice as a convenient and simple method for diagnosing and monitoring the condition of patients. The analysis of biomarkers has found its niche in oncology; however, their application in cardiovascular diseases is still in its infancy. Studies on apelin indicate the potential diagnostic and prognostic significance of the assessment of this marker in patients with cardiovascular diseases. The beneficial effect of apelin on the heart and blood vessels allows us to consider this marker as a therapeutic target. The combination of apelin with other biological markers, particularly brain natriuretic peptide and its precursor, may increase the predictive value of apelin.

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Promising novel therapeutic targets for kidney disease: Emphasis on kidney-specific proteins

Cited by 5 publications

References 89 publications

Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence

Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence

Oxidative stress and NRF2 signaling in kidney injury

Diagnostic, prognostic and therapeutic aspects of apelin in cardiovascular diseases

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