Inflammatory Cytokines in Diabetic Kidney Disease: Pathophysiologic and Therapeutic Implications

Donate‐Correa, Javier; Ferri, Carla; Sánchez-Quintana, Fátima; Pérez-Castro, Atteneri; González-Luis, Ainhoa; Martín‐Núñez, Ernesto; Mora‐Fernández, Carmen; Navarro‐González, Juan F.

doi:10.3389/fmed.2020.628289

Cited by 66 publications

(56 citation statements)

References 118 publications

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“…Some studies have shown that inflammation markers and oxidative stress are elevated in patients with chronic kidney disease and the present study shows an association between inflammatory markers and reduced renal function in cases of HEmerg [11,38]. Similarly, inflammatory cytokines are predictors of the initiation and progression of diabetic kidney disease, regulating the immune response and exerting important actions as effectors of lesions, including the development of nephropathy [39]. In the present work, all the cytokines were higher in the HC group compared to control groups.…”

Section: Discussionsupporting

confidence: 66%

Inflammatory Cytokines are Associated to Lower Glomerular Filtration Rate in Patients with Hypertensive Emergency

Andrade

Aguiar

Mansor

et al. 2021

Preprint

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Introduction: Hypertension and kidney function are closely related. However, there are few studies on renal function during acute elevation of blood pressure (BP), denominated hypertensive crisis (HC). Objectives: To evaluate the relationship between renal function and inflammatory cytokines in HC, subdivided into hypertensive urgency (HUrg) and emergency (HEmerg). Methods: 74 normotensive subjects (NT), 74 controlled hypertensive (ContrHT), 50 patients with HUrg and 78 with HEmerg were studied. The glomerular filtration rate (eGFR) was estimated, and cytokine levels were measured. Statistical analysis was performed using the Kruskal-Wallis or Mann-Whitney test and Spearman's correlation, with significant differences p-value <0.05. Results: The eGFR was significantly lower in HEmerg group compared to the NT, ContrHT and HUrg groups. All cytokines were significantly elevated in patients with HC compared to the control groups (NT and ContrHT). In addition, the cytokines interleukin (IL)-1β, IL-6 and IL-10 were higher in the HEmerg group compared to the HUrg groups. There was a negative correlation between eGFR and the cytokines (IL-6, IL-8, IL-10 and TNF-α) in the HEmerg group. Conclusions: Elevated inflammatory cytokines are associated with reduced eGFR in individuals with HEmerg, indicating an involvement of the inflammatory process in the pathogenesis of acute elevations of BP.

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Section: Discussionsupporting

confidence: 66%

Inflammatory Cytokines are Associated to Lower Glomerular Filtration Rate in Patients with Hypertensive Emergency

Andrade

Aguiar

Mansor

et al. 2021

Preprint

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“…TNFα concentration was enhanced even in tear fluids, which correlated well with the severity of diabetic retinopathy [31]. Increased TNFα levels have been related to the development of diabetic nephropathy involving reactive oxygen species accumulation and related cytotoxicity in kidney cells [32][33][34]), while TNFα inhibition ameliorated the glomerular and tubular injury in diabetic kidney [35]. TNFα is directly involved in the destruction of β-cells in isolated islets [36] and plays a key role in the onset of diabetes in mice through the regulation of dendritic cell maturation and activation of islet-specific pancreatic T-cells [37].…”

Section: Introductionmentioning

confidence: 94%

Intestinal Region-Specific and Layer-Dependent Induction of TNFα in Rats with Streptozotocin-Induced Diabetes and after Insulin Replacement

Bódi

Chandrakumar

Doghmi

et al. 2021

Cells

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Tumour necrosis factor alpha (TNFα) is essential in neuroinflammatory modulation. Therefore, the goal of this study is to reveal the effects of chronic hyperglycaemia and insulin treatment on TNFα expression in different gut segments and intestinal wall layers. TNFα expression was mapped by fluorescent immunohistochemistry and quantitative immunogold electron microscopy in myenteric ganglia of duodenum, ileum and colon. Tissue TNFα levels were measured by enzyme-linked immunosorbent assays in muscle/myenteric plexus-containing (MUSCLE-MP) and mucosa/submucosa/submucous plexus-containing (MUC-SUBMUC-SP) homogenates. Increasing density of TNFα-labelling gold particles is observed in myenteric ganglia from proximal to distal segments and TNFα tissue levels are much more elevated in MUSCLE-MP homogenates than in MUC-SUBMUC-SP samples in healthy controls. In the diabetics, the number of TNFα gold labels is significantly increased in the duodenum, decreased in the colon and remained unchanged in the ileal ganglia, while insulin does not prevent these diabetes-related TNFα changes. TNFα tissue concentration is also increased in MUSCLE-MP homogenates of diabetic duodenum, while decreased in MUC-SUBMUC-SP samples of diabetic ileum and colon. These findings support that type 1 diabetes has region-specific and intestinal layer-dependent effects on TNFα expression, contributing to the regional damage of myenteric neurons and their intestinal milieu.

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“…There is growing evidence that kidney inflammation plays a vital role in the occurrence and development of DKD [ 3 ]. Inflammation and oxidative stress are strongly correlated with the risk of developing DKD [ 4 – 6 ]. Immune cell infiltration (mainly macrophages) of renal tissue is increased in both animal models and patients with DKD [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis

Song

Wang

et al. 2022

Cell Death Dis

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Renal inflammation is a critical pathophysiological characteristic of diabetic kidney disease (DKD). The mechanism of the inflammatory response is complicated, and there are few effective treatments for renal inflammation that can be used clinically. Insulin-like growth factor-binding protein 5 (IGFBP5) is an important secretory protein that is related to inflammation and fibrosis in several tissues. Studies have shown that the IGFBP5 level is significantly upregulated in DKD. However, the function of IGFBP5 and its mechanism in DKD remain unclear. Here, we showed that IGFBP5 levels were significantly increased in the kidneys of diabetic mice. Ablation of IGFBP5 alleviated kidney inflammation in DKD mice. Mechanistically, IGFBP5 increased glycolysis, which was characterized by increases in lactic acid and the extracellular acidification rate, by activating the transcription factor early growth response 1 (EGR1) and enhancing the expression of PFKFB3 in endothelial cells. Furthermore, a mutation in PFKFB3 attenuated renal inflammation in DKD mice. Taken together, we provided evidence that IGFBP5 enhanced kidney inflammation through metabolic reprogramming of glomerular endothelial cells. Our results provide new mechanistic insights into the effect of IGFBP5 on kidney and highlight potential therapeutic opportunities for IGFBP5 and the metabolic regulators involved in DKD.

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Inflammatory Cytokines in Diabetic Kidney Disease: Pathophysiologic and Therapeutic Implications

Cited by 66 publications

References 118 publications

Inflammatory Cytokines are Associated to Lower Glomerular Filtration Rate in Patients with Hypertensive Emergency

Inflammatory Cytokines are Associated to Lower Glomerular Filtration Rate in Patients with Hypertensive Emergency

Intestinal Region-Specific and Layer-Dependent Induction of TNFα in Rats with Streptozotocin-Induced Diabetes and after Insulin Replacement

IGFBP5 promotes diabetic kidney disease progression by enhancing PFKFB3-mediated endothelial glycolysis

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