Urinary IL-18 is associated with arterial stiffness in patients with type 2 diabetes

Shi, Caifeng; He, Aiqin; Wang, Xiaomei; Wang, Lulu; Zhu, Xueting; Jiang, Lei; Yang, Junwei; Zhang, Yang

doi:10.3389/fendo.2022.956186

Cited by 5 publications

(2 citation statements)

References 23 publications

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“… 15 IL-18, a pro-inflammatory marker, is positively correlated with the level of proteinuria in DKD patients 16 and is a biomarker for renal tubule injury and repair. 17 NOD-like receptors (NLRPs and NLRCs) are activated in the diabetic micropig model to promote the expression of downstream inflammatory factors such as IL-6 and IL-18 through TGF-β pathway, causing metabolic inflammation of kidney tissue, and ultimately leading to the occurrence and development of diabetic kidney disease. 18 In this experiment, we found that the serum levels of TGF-β, IL-6 and IL-18 in diabetic kidney disease patients were significantly higher than those in normal diabetic albuminuria group and healthy control group, and were significantly higher in diabetic microalbuminuria.…”

Section: Discussionmentioning

confidence: 99%

The Expression of miR-377-3p in Patients with DKD and the Regulatory Mechanism of miR-377-3p on the Inflammatory Response of HK-2 Cells Through TGF-β

Xing,

Lu,

Liu

et al. 2024

DMSO

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Objective The purpose of the study was to investigate the expression levels and correlation of inflammatory factors such as miR-377-3p and TGF-β in patients with diabetic kidney disease (DKD), and to investigate the regulatory mechanism of transfection of miR-377-3p on the inflammatory response of HK-2 cell induced by high glucose. Methods According to UACR, patients were divided into normal albuminuria group (Con, n = 29), microalbuminuria group (Micro, n = 31) and macroalbuminuria group (Macro, n = 30), analyzed the correlation and influencing factors between DKD and inflammatory factor. HK-2 cells were randomly divided into four groups: normal control group (NC), high glucose group (HG), miR-377-3p overexpression group (MIN), and miR-377-3p inhibition group (IN). After transfection of miR-377-3p mimics and inhibitors, the contents of TGF-β, IL-6 and IL-18 were detected by RT-PCR and Western blot. Results The levels of miR-377-3p, TGF-β, IL-6 and IL-18 in both Micro group and Macro group were significantly higher than those in Con group (P < 0.05); Pearson correlation analysis showed that miR-377-3p was positively correlated with UACR, TG, TGF-β, IL-6 and IL-18, and negatively correlated with GFR (P < 0.05). Cell experiment: RT-PCR and Western blot results showed that miR-377-3p, TGF-β, IL-6 and IL-18 in HG group were significantly higher than those in NC group (P < 0.05). After transfection with miR-377-3p inhibitor, the levels of miR-377-3p, TGF-β, IL-6 and IL-18 in IN group were significantly decreased compared with HG group and MIN group. Conclusion miR-377-3p expression was elevated both in serum of DKD patients and in HK-2 cells with high glucose induced injury, overexpression of miR-377-3p exacerbates the damage to HK-2 cells and promotes the progression of DKD. Silencing miR-377-3p can potentially regulate the levels of inflammatory factors in HK-2 cells by targeting downregulation of TGF-β expression, thereby mitigating the damage to HK-2 cells and delaying the development of diabetic kidney disease.

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Section: Discussionmentioning

confidence: 99%

The Expression of miR-377-3p in Patients with DKD and the Regulatory Mechanism of miR-377-3p on the Inflammatory Response of HK-2 Cells Through TGF-β

Xing,

Lu,

Liu

et al. 2024

DMSO

View full text Add to dashboard Cite

show abstract

“…The average of two separate measurements of systolic and diastolic BP was recorded. A third measurement was be taken if a BP difference ≥ 10 mmHg for systolic BP or ≥ 5 mmHg for diastolic BP occurred with the two closest BP measurements averaged and recorded [ 13 ]. Hypertension was diagnosed for those with systolic BP > 140 mmHg or diastolic BP > 90 mmHg or on antihypertension medication [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

Clusters of Body Fat and Nutritional Parameters are Strongly Associated with Diabetic Kidney Disease in Adults with Type 2 Diabetes

He,

Shi,

et al. 2023

Diabetes Ther

Self Cite

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Introduction Diabetic kidney disease (DKD) has become the leading cause of chronic kidney disease and end-stage renal failure in most developed and many developing countries. Strategies aimed at identifying potential modifiable risk factors for DKD are urgently needed. Here, we investigated the association between clusters of body fat and nutritional parameters with DKD in adults with type 2 diabetes mellitus (T2DM). Methods This was a cross-sectional study of 184 participants with T2DM. Biochemical parameters including fasting blood glucose, hemoglobin A1c, hemoglobin, albumin, creatinine, and urinary albumin-to-creatinine ratio (UACR) were measured. The data for percentage of body fat mass (PBF), visceral fat area (VFA), phase angle at 50 kHz (PA50), and body cell mass (BCM) were obtained by bioelectrical impedance analysis (BIA). DKD was diagnosed by UACR and estimated glomerular filtration rate. Factor analysis was used for dimensionality reduction clustering among variables. The association of clusters with the presence of DKD was assessed using binary logistic regression analysis. Results Factor analysis identified two clusters which were interpreted as a body fat cluster with positive loadings of VFA, body mass index, waist circumstance, and PBF and a nutritional parameters cluster with positive loadings of PA50, hemoglobin, BCM, and albumin. Participants were divided into the four groups based on the sex-specific cutoff value (median) of each cluster score calculated using the cluster weights and the original variable values. Only participants with high body fat and poor nutritional parameters (OR 3.43, 95% CI 1.25–9.42) were associated with increased odds of having DKD. Conclusion Body fat and nutritional parameters were strongly associated with and considerably contributed to the presence of DKD, suggesting that body fat and nutrition might be promising markers representing metabolic state in pathogenesis of DKD and clinical utility of BIA might provide valuable recommendations to patients with T2DM.

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Urinary metabolites associate with the presence of diabetic kidney disease in type 2 diabetes and mediate the effect of inflammation on kidney complication

Shi,

Wan,

et al. 2023

Acta Diabetol

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Aims Diabetic kidney disease (DKD) is the one of the leading causes of end-stage kidney disease. Unraveling novel biomarker signatures capable to identify patients with DKD is favorable for tackle the burden. Here, we investigated the possible association between urinary metabolites and the presence of DKD in type 2 diabetes (T2D), and further, whether the associated metabolites improve discrimination of DKD and mediate the effect of inflammation on kidney involvement was evaluated. Methods Two independent cohorts comprising 192 individuals (92 DKD) were analyzed. Urinary metabolites were analyzed by targeted metabolome profiling and inflammatory cytokine IL-18 were measured by ELISA. Differentially expressed metabolites were selected and mediation analysis was carried out. Results Seven potential metabolite biomarkers (i.e., S-Adenosyl-L-homocysteine, propionic acid, oxoadipic acid, leucine, isovaleric acid, isobutyric acid, and indole-3-carboxylic acid) were identified using the discovery and validation design. In the pooled analysis, propionic acid, oxoadipic acid, leucine, isovaleric acid, isobutyric acid, and indole-3-carboxylic acid were markedly and independently associated with DKD. The composite index of 7 potential metabolite biomarkers (CMI) mediated 32.99% of the significant association between the inflammatory IL-18 and DKD. Adding the metabolite biomarkers improved the discrimination of DKD. Conclusions In T2D, several associated urinary metabolites were identified to improve the prediction of DKD. Whether interventions aimed at reducing CMI also reduce the risk of DKD especially in patients with high IL-18 needs further investigations.

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Urinary IL-18 is associated with arterial stiffness in patients with type 2 diabetes

Cited by 5 publications

References 23 publications

The Expression of miR-377-3p in Patients with DKD and the Regulatory Mechanism of miR-377-3p on the Inflammatory Response of HK-2 Cells Through TGF-β

The Expression of miR-377-3p in Patients with DKD and the Regulatory Mechanism of miR-377-3p on the Inflammatory Response of HK-2 Cells Through TGF-β

Clusters of Body Fat and Nutritional Parameters are Strongly Associated with Diabetic Kidney Disease in Adults with Type 2 Diabetes

Urinary metabolites associate with the presence of diabetic kidney disease in type 2 diabetes and mediate the effect of inflammation on kidney complication

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