Syndecan-1 and Free Indoxyl Sulfate Levels Are Associated with miR-126 in Chronic Kidney Disease

Fourdinier, Ophélie; Glorieux, Griet; Brigant, Benjamin; Pletinck, Anneleen; Vanholder, Raymond; Choukroun, Gabriel; Verbeke, Francis; Massy, Ziad A.; Meuth, Valérie Metzinger-Le

doi:10.3390/ijms221910549

Cited by 16 publications

(12 citation statements)

References 39 publications

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“…A meta-analysis comprising data from 11 studies revealed that indoxyl sulfate and p-cresyl sulfate were found to be independently linked to an increased risk of cardiovascular events and mortality in patients with CKD [72]. Another study suggests that only indoxyl sulfate, and not p-cresyl sulfate signaling, can be linked to altered miR-126 expression, which has been implicated in vascular endothelial functions, angiogenesis, and consequently the pathogenesis of CKD [73].…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…The quantitative polymerase chain reaction (qPCR) reactions were performed on a 7900HT Standard Real‐Time PCR System (Applied Biosystems Inc.) thorough the miScript SYBR Green PCR Kit (Qiagen). miR‐144‐5p expression was estimated using the 2 −ΔΔ C t method [14]. RNA was extracted from rat serum and kidney tissue for RT‐qPCR.…”

Section: Methodsmentioning

confidence: 99%

Clinical expression of microRNA‐144‐5p and its regulatory effect on renal function in uremia

Zang

Li²,

Zhou

2022

Ther Apher Dial

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Objective The study commits to probing the clinical expression of microRNA‐144‐5p (miR‐144‐5p) and its modulatory effect on the renal function of uremia. Methods Levels of blood urea nitrogen (BUN), β2‐microglobulin (β2‐MG), serum creatinine (Scr), blood calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) and miR‐144‐5p expression in serum of uremia patients were detected. The correlation among miR‐144‐5p expression with BUN, β2‐MG, Scr, Ca, P, and iPTH levels in uremic patients was analyzed. The rats were injected with miR‐144‐5p agomir to detect the change of BUN, Scr, β2‐MG, Scr, Ca, P, and iPTH levels in uremic rats. Results miR‐144‐5p expression in uremic patients was negatively correlated with BUN, Scr, β2‐MG, P, and iPTH levels, and positively correlated with free Ca concentration in blood. miR‐144‐5p elevation reduced BUN, Scr, β2‐MG, P, and iPTH levels, and increased free Ca concentration in blood in uremic rats. Conclusion miR‐144‐5p is lowly expressed, and miR‐144‐5p has a regulatory effect on renal function in uremia.

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“…The effect of several uremic toxins on vascular dysfunction may also be due to their ability to modulate the downstream expression of many intracellular miRNAs in endothelial cells [ 73 , 74 ]. Altogether, this evidence highlights that uremic toxins may represent the missing player between endothelial damage and uremia-related CVI.…”

Section: The Gut–kidney Axismentioning

confidence: 99%

Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives

Caggiano

Stasi

Franzin

et al. 2023

Toxins

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During the past decades, the gut microbiome emerged as a key player in kidney disease. Dysbiosis-related uremic toxins together with pro-inflammatory mediators are the main factors in a deteriorating kidney function. The toxicity of uremic compounds has been well-documented in a plethora of pathophysiological mechanisms in kidney disease, such as cardiovascular injury (CVI), metabolic dysfunction, and inflammation. Accumulating data on the detrimental effect of uremic solutes in kidney disease supported the development of many strategies to restore eubiosis. Fecal microbiota transplantation (FMT) spread as an encouraging treatment for different dysbiosis-associated disorders. In this scenario, flourishing studies indicate that fecal transplantation could represent a novel treatment to reduce the uremic toxins accumulation. Here, we present the state-of-the-art concerning the application of FMT on kidney disease to restore eubiosis and reverse the retention of uremic toxins.

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Syndecan-1 and Free Indoxyl Sulfate Levels Are Associated with miR-126 in Chronic Kidney Disease

Cited by 16 publications

References 39 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

Clinical expression of microRNA‐144‐5p and its regulatory effect on renal function in uremia

Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives

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