Serum interleukin-6 levels predict kidney disease progression in diabetic nephropathy

Sánchez‐Álamo, Beatriz; Shabaka, Amir; Cachofeiro, Victoria; Cases-Corona, Clara; Fernández-Juárez, Gema

doi:10.5414/cn110223

Cited by 35 publications

(15 citation statements)

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“…Researchers have observed higher levels of this interleukin in patients diagnosed with DN compared to diabetic patients who did not develop nephropathy [ 236 ]. This was also confirmed by other literature reports, which indicated that the functional and structural abnormalities in the course of DN and the progression of kidney damage are related to IL-6 [ 237 , 238 , 239 , 240 ]. Additionally, in the case of analyses carried out in animal models (rats) with diabetes, in whom the level of IL-6 mRNA in the renal cortex was determined, a positive correlation was shown related to the concentration of this cytokine in urine [ 235 ].…”

Section: The Importance Of Interleukins In Kidney Diseasessupporting

confidence: 89%

Biological Role, Mechanism of Action and the Importance of Interleukins in Kidney Diseases

Mertowska

Mertowski

Smarz-Widelska³

et al. 2022

IJMS

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Each year, the number of patients who are diagnosed with kidney disease too late is increasing, which leads to permanent renal failure. This growing problem affects people of every age, sex and origin, and its full etiopathogenesis is not fully understood, although the involvement of genetic susceptibility, infections, immune disorders or high blood pressure is suggested. Difficulties in making a correct and quick diagnosis are caused by the lack of research on early molecular markers, as well as educational and preventive activities among the public, which leads to the late detection of kidney diseases. An important role in the homeostasis and disease progression, including kidney diseases, is attributed to interleukins, which perform several biological functions and interact with other cells and tissues of the body. The aim of this article was to systematize the knowledge about the biological functions performed by interleukins in humans and their involvement in kidney diseases development. In our work, we took into account the role of interleukins in acute and chronic kidney disease and kidney transplantation.

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Section: The Importance Of Interleukins In Kidney Diseasessupporting

confidence: 89%

Biological Role, Mechanism of Action and the Importance of Interleukins in Kidney Diseases

Mertowska

Mertowski

Smarz-Widelska³

et al. 2022

IJMS

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“…GDF15 was responsible for inflammatory pathways involved in regulating cell apoptosis, repair, and proliferation and was found to be elevated as CKD progression [51]. Interleukin-6, encoded by IL6, is a pleiotropic cytokine and was found to contribute to acute and chronic kidney injury and fibrosis [52]. After kidney stress injury or cell damage, renal tubular cells enter the G1 phase and cell-cycle arrest occurs accompanied by the accumulation of damaged DNA [53,54].…”

Section: Discussionmentioning

confidence: 99%

Urinary Galectin-3 as a Novel Biomarker for the Prediction of Renal Fibrosis and Kidney Disease Progression

Tsai

Chen

et al. 2022

Biomedicines

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Plasma galectin-3 (Gal-3) is associated with organ fibrosis, but whether urinary Gal-3 is a potential biomarker of kidney disease progression has never been explored. Between 2018 and 2021, we prospectively enrolled 280 patients who underwent renal biopsy and were divided into three groups based on their urinary Gal-3 levels (<354.6, 354.6–510.7, and ≥510.8 pg/mL) to assess kidney disease progression (defined as ≥40% decline in the estimated glomerular filtration rate or end-stage renal disease) and renal histology findings. Patients in the highest urinary Gal-3 tertile had the lowest eGFRs and highest proteinuria levels. In multivariate Cox regression models, patients in the highest tertile had the highest risk of kidney disease progression (adjusted hazard ratio, 4.60; 95% confidence interval, 2.85–7.71) compared to those in the lowest tertile. Higher urinary Gal-3 levels were associated with more severe renal fibrosis. Intrarenal mRNA expression of LGALS3 (Gal-3-encoded gene) was most correlated with the renal stress biomarkers (IGFBP7 and TIMB2), renal function biomarkers (PTGDS) and fibrosis-associated genes (TGFB1). The urinary Gal-3 level may be useful for the identification of patients at high risk of kidney disease progression and renal fibrosis, and for the early initiation of treatments for these patients.

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“…Fifth, IL-6 and TNFα mRNA levels in tissue of participants should be provided, instead of the serum IL-6 and TNFα levels used in this study. However, serum IL-6 and TNFα have been reported to be used as predictors of kidney disease progression in diabetic nephropathy [ 34 , 35 ]. Moreover, the variation tendency of levels of serum inflammatory factors in participants was similar to that of mRNA expression of inflammatory factors in in vivo and in vitro studies in the present study.…”

Section: Discussionmentioning

confidence: 99%

SETD8 cooperates with MZF1 to participate in hyperglycemia-induced endothelial inflammation via elevation of WNT5A levels in diabetic nephropathy

Wang

Hou

et al. 2022

Cell Mol Biol Lett

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Objective Diabetic nephropathy (DN) is regarded as the main vascular complication of diabetes mellitus, directly affecting the outcome of diabetic patients. Inflammatory factors were reported to participate in the progress of DN. Wingless-type family member 5 (WNT5A), myeloid zinc finger 1 (MZF1), and lysine methyltransferase 8 (SETD8) have also been reported to elevate inflammatory factor levels and activate the nuclear factor kappa B (NF-κB) pathway to induce endothelial dysfunction. In the current study, it was assumed that MZF1 associates with SETD8 to regulate WNT5A transcription, thus resulting in hyperglycemia-induced glomerular endothelial inflammation in DN. Methods The present study recruited 25 diagnosed DN patients (type 2 diabetes) and 25 control participants (nondiabetic renal cancer patients with normal renal function, stage I–II) consecutively. Moreover, a DN rat and cellular model was constructed in the present study. Immunohistochemistry, Western blot, and quantitative polymerase chain reaction (qPCR) were implemented to determine protein and messenger RNA (mRNA) levels. Coimmunoprecipitation (CoIP) and immunofluorescence were implemented in human glomerular endothelial cells (HGECs). Chromatin immunoprecipitation assays and dual luciferase assays were implemented to determine transcriptional activity. Results The results of this study indicated that levels of WNT5A expression, p65 phosphorylation (p-p65), and inflammatory factors were all elevated in DN patients and rats. In vitro, levels of p-p65 and inflammatory factors increased along with the increase of WNT5A expression in hyperglycemic HGECs. Moreover, high glucose increased MZF1 expression and decreased SETD8 expression. MZF1 and SETD8 inhibit each other under the stimulus of high glucose, but cooperate to regulate WNT5A expression, thus influencing p-p65 and endothelial inflammatory factors levels. Overexpression of MZF1 and silencing of SETD8 induced endothelial p-p65 and inflammatory factors levels, which can be reversed by si-WNT5A. Mechanistic research indicated that MZF1, SETD8, and its downstream target histone H4 lysine 20 methylation (H4K20me1) all occupied the WNT5A promoter region. sh-SETD8 expanded the enrichment of MZF1 on WNT5A promoter. Our in vivo study proved that SETD8 overexpression inhibited levels of WNT5A, p-p65 expression, and inflammatory factors in DN rats. Conclusions MZF1 links with SETD8 to regulate WNT5A expression in HGECs, thus elevating levels of hyperglycemia-mediated inflammatory factors in glomerular endothelium of DN patients and rats. Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548

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Serum interleukin-6 levels predict kidney disease progression in diabetic nephropathy

Cited by 35 publications

References 0 publications

Biological Role, Mechanism of Action and the Importance of Interleukins in Kidney Diseases

Biological Role, Mechanism of Action and the Importance of Interleukins in Kidney Diseases

Urinary Galectin-3 as a Novel Biomarker for the Prediction of Renal Fibrosis and Kidney Disease Progression

SETD8 cooperates with MZF1 to participate in hyperglycemia-induced endothelial inflammation via elevation of WNT5A levels in diabetic nephropathy

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