The IL-8-CXCR1/2 axis contributes to diabetic kidney disease

Loretelli, Cristian; Rocchio, Francesca; D’Addio, Francesca; Nasr, Moufida Ben; Castillo‐Leon, Eduardo; Dellepiane, Sergio; Vergani, Andrea; Abdelsalam, Ahmed; Assi, Emma; Maestroni, Anna; Usuelli, Vera; Bassi, Roberto; Pastore, Ida; Yang, Jun; Essawy, Basset El; Elased, Khalid M.; Fadini, Gian Paolo; Ippolito, Elio; Seelam, Andy Joe; Pezzolesi, Marcus G.; Corradi, Domenico; Zuccotti, Gian Vincenzo; Gallieni, Maurizio; Allegretti, Marcello; Niewczas, Monika A.

doi:10.1016/j.metabol.2021.154804

Cited by 28 publications

(34 citation statements)

References 31 publications

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“…High concentrations of glucose induce the secretion of inflammatory cytokine MCP‐1 and leukocyte interleukin‐8 (IL‐8) by activating the reactive oxygen species (ROS) and NF‐κB pathways 5,6 . High serum levels of MCP‐1 and IL‐8 accelerate the progression of diabetes and increase the incidence of complications 7‐9 . As a result, therapeutic agents against ROS have also been widely studied in the treatments of diabetes mellitus 10 …”

Section: Introductionmentioning

confidence: 99%

Effect of vitamin D on oxidative stress and serum inflammatory factors in the patients with type 2 diabetes

WeiGang

et al. 2022

Clinical Laboratory Analysis

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The type 2 diabetes mellitus (T2DM) is an urgent global health problem. T2DM patients are in a state of high oxidative stress and inflammation. Vitamin D and glutathione (GSH) play crucial roles in antioxidation and anti‐inflammation. However, T2DM patients have lower vitamin D and GSH levels than healthy persons. A randomized controlled trial was conducted to see the effect of the vitamin D supplementation on oxidative stress and inflammatory factors in T2DM patients. In this study, a total of 178 T2DM patients were randomly enrolled, 92 patients received regular treatment (T2DM group) and 86 patients in Vitamin D group received extra vitamin D 400 IU per day in addition to regular treatment. Serum vitamin D, GSH, GSH metabolic enzyme GCLC and GR, inflammatory factor MCP‐1, and IL‐8 levels were investigated. We found that the T2DM group has significantly higher concentrations of MCP‐1 and IL‐8 than those in the healthy donor group. After vitamin D supplementation for 90 days, T2DM patients had a 2‐fold increase of GSH levels, from 2.72 ± 0.84 to 5.76 ± 3.19 μmol/ml, the concentration of MCP‐1 decreased from 51.11 ± 20.86 to 25.42 ± 13.06 pg/ml, and IL‐8 also decreased from 38.21 ± 21.76 to 16.05 ± 8.99 pg/ml. In conclusion, our study demonstrated that vitamin D could regulate the production of GSH, thereby reducing the serum levels of MCP‐1 and IL‐8, alleviating oxidative stress and inflammation, providing evidence of the necessity and feasibility of adjuvant vitamin D treatment among patients with T2DM. On the other hand, vitamin D and GSH levels have important diagnostic and prognostic values in T2DM patients.

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Section: Introductionmentioning

confidence: 99%

Effect of vitamin D on oxidative stress and serum inflammatory factors in the patients with type 2 diabetes

WeiGang

et al. 2022

Clinical Laboratory Analysis

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“…Increasing studies have confirmed that immune inflammation, especially innate immunity, plays a vital role in the pathogenesis of DKD, including tumor necrosis factor receptor superfamily members, interleukin-8-CXCR1/2 axis and immune-related molecule B7-1. [10][11][12] As a central component of innate immunity, the complement overactivation participates in DKD progression. [13][14][15][16][17][18] In our previous study, it was found that patients with C3c deposition in the kidney had more severe renal injury, including lower eGFR, and higher scores for IFTA.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging experimental and clinical evidence reported the crucial role of renal inflammation in the pathogenesis and progression of DKD 10‐12 . The complement system, as an essential component of human immune system, was proved to participate in the development of DKD 13‐18 .…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Emerging experimental and clinical evidence reported the crucial role of renal inflammation in the pathogenesis and progression of DKD. [10][11][12] The complement system, as an essential component of human immune system, was proved to participate in the development of DKD. [13][14][15][16][17][18] Targeting complement overactivation can improve renal function and ameliorate renal fibrosis in animal models of DKD.…”

Section: Introductionmentioning

confidence: 99%

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C3c deposition predicts worse renal outcomes in patients with biopsy‐proven diabetic kidney disease in type 2 diabetes mellitus

Sun

Chang

et al. 2022

Journal of Diabetes

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Background Although extensive efforts have been paid to identify reliable predictors for renal outcomes of diabetic kidney disease (DKD) patients in type 2 diabetes mellitus (T2DM), there are still only a limited number of predictive factors for DKD progression. Increasing evidence reported the role of the overactivated complement system in the pathogenesis of DKD. Whether renal complement depositions are associated with renal outcomes of DKD in T2DM is of interest. Methods A total of 213 biopsy‐proven DKD patients with T2DM were retrospectively recruited. Clinical and pathological data of the patients were analyzed. Kaplan‐Meier analysis and Cox regression analysis were performed to explore predictors of end‐stage renal disease (ESRD). Results During a median follow‐up of 23.0 (12.0, 39.0) months, 100/213 (46.9%) patients progressed to ESRD. C3c and C1q deposition were observed in 133/213 (62.4%) and 45/213 (21.1%) patients, respectively. Kaplan‐Meier analysis revealed patients with C3c or C1q deposition had significantly worse renal outcomes compared with those without C3c or C1q deposition (p = .001 and p < .001, respectively). Univariate and multivariate Cox regression analysis demonstrated proteinuria (per 1 g/24 h increase, hazard ratio [HR] 1.134, 95% confidence interval [CI] [1.079, 1.191], p < .001), interstitial fibrosis and tubular atrophy score (score 2 and 3 vs. 0 and 1, HR 3.925, 95% CI [1.855, 8.304], p < .001), and C3c deposition (per 1+ increase, HR 1.299, 95% CI [1.073, 1.573], p = .007) were independent predictors for ESRD in DKD patients with T2DM. Conclusions C3c deposition in the kidney was associated with worse renal outcomes and was an independent predictor for ESRD in DKD patients with T2DM.

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“…Hyperglycemia could increase interleukin (IL)-1β, IL-6, or IL-12 which are involved in the progression of DKD ( Chen et al., 2004 , Ha et al., 2002 , Mima, 2013 , Myint et al., 2006 , Wu et al., 2010 ). Further, recent study showed that hyperglycemia activated IL8-CXCR1/2 axis, inducing podocyte damage in DKD ( Loretelli et al., 2021 ). Interestingly, podocytes have shown to express Toll-like receptor 4 (TLR4), and stimulation with TLR4-specific ligands induces the costimulatory molecule B7-1.…”

Section: The Effects Of Inflammatory Processes On Dkdmentioning

confidence: 99%

Mitochondria-targeted drugs for diabetic kidney disease

Mima

2022

Heliyon

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Diabetic kidney disease (DKD) is one of the most frequent causes of chronic kidney disease (CKD) in the United States. Chronic hyperglycemic conditions are thought to be the primary cause of DKD. However, it is clinically difficult to achieve glycemic control in individuals with diabetes. Recent advances in mitochondrial biology have provided a new understanding of mitochondrial dysfunction in DKD. Studies have revealed impaired mitochondrial function in a variety of diabetic complications, including DKD; moreover, abnormal mitochondrial fission may be involved in the progression of DKD. It has been reported that metformin or sodium-glucose cotransporter 2 (SGLT2) inhibitors may provide renal protection by improving mitochondrial dynamics and reducing oxidative stress. Thus, drugs that target the restoration of mitochondrial function may become novel therapeutic agents for DKD. Imeglimin is the first in a new class of oral antidiabetic drugs that can reduce reactive oxygen species production and increase mitochondrial DNA synthesis. This review outlines the potential therapeutic interventions that affect mitochondrial function and prevent DKD.

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The IL-8-CXCR1/2 axis contributes to diabetic kidney disease

Cited by 28 publications

References 31 publications

Effect of vitamin D on oxidative stress and serum inflammatory factors in the patients with type 2 diabetes

Effect of vitamin D on oxidative stress and serum inflammatory factors in the patients with type 2 diabetes

C3c deposition predicts worse renal outcomes in patients with biopsy‐proven diabetic kidney disease in type 2 diabetes mellitus

Mitochondria-targeted drugs for diabetic kidney disease

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