Inflammatory Cytokines in Diabetic Nephropathy

Donate-Correa, Javier; Martín‐Núñez, Ernesto; Muros‐de‐Fuentes, Mercedes; Mora‐Fernández, Carmen; Navarro‐González, Juan F.

doi:10.1155/2015/948417

Cited by 219 publications

(197 citation statements)

References 124 publications

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“…The primary risk factors contributing to the development and/or progression of DN include hyperglycemia, hypertension and dyslipidemia (18). The occurrence of DN is predominantly mediated by high glucose levels and microvascular hemodynamic changes and is further mediated by a variety of inflammatory cytokines in diabetic kidneys, which activate the inflammatory pathways (19). Capillary basement membrane thickening and mesangial matrix expansion of glomerular sclerosis precedes the final stages of DN (20).…”

Section: Discussionmentioning

confidence: 99%

Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-κB pathway

Zhang

Gao

et al. 2017

Exp Ther Med

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Abstract. The present study investigated the mechanism underlying the anti-inflammatory effects of Tangshen formula (TS) in Sprague Dawley (SD) rats with diabetic nephropathy (DN). A rat model of DN was established by intraperitoneal injection of 1% (40 mg/kg) streptozotocin and administration of a high fat and glucose diet. Subsequently, SD rats were randomly divided into six groups (n=8): A DN group, a valsartan group, a high-dose TS group, a middle-dose TS group, a low-dose TS group and a control group with normal SD rats. Once rats received their allocated treatment for 12 weeks, body weight and kidney weight were recorded, and fasting blood glucose, ratio of urinary protein, β 2 -MG and creatinine clearance rate were determined. Furthermore, hemodynamic indices, including plasma viscosity and whole blood reduction viscosity were detected. Immunohistochemistry was used to detect the infiltration of macrophages in the kidneys of rats. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to investigate the activation; mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), nuclear factor-κB (NF-κB) and sirtuin-1 (SIRT1) in each group. In comparison with the DN group, each biochemical indicator of rats in the high-dose TS group was significantly decreased (P<0.05). Blood viscosity in each treatment group was significantly decreased when compared with the DN group (P<0.01). Hematoxylin and eosin staining indicated that the infiltration of macrophages was significantly decreased in the high-dose TS group when compared with the DN group (P<0.01). mRNA and protein expression levels of MCP-1 and MIF in the high-dose TS group were significantly decreased when compared with the DN group (P<0.05). In the treatment groups, SITR1 mRNA expression levels were significantly increased, whereas the mRNA expression levels of NF-κB were significantly decreased (P<0.01). Western blotting results indicated a significant decrease in the protein expression levels of acetylated NF-κB in the treatment groups when compared with the DN group (P<0.01) and the propensity of protein expression of the other inflammatory factors were consistent with the mRNA findings. The results of the high-dose TS group were similar to those of the valsartan group. The present study indicates that TS was able to activate SITR1, which lead to NF-κB deacetylation, thus reducing the release of inflammatory factors and decreasing the severity of diabetic nephropathy.

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Section: Discussionmentioning

confidence: 99%

Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-κB pathway

Zhang

Gao

et al. 2017

Exp Ther Med

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“…Additionally, comorbidities, often seen in connection with ESRD, such as congestive heart failure, diabetes mellitus, hypertension, and aging-related changes in the immune response may further enhance a chronic inflammatory state. Plasma concentrations of inflammatory molecules, including pro-inflammatory cytokines, are elevated in diabetic patients, and they increase as diabetic nephropathy progresses [10] . Increases in arterial blood pressure and pulse pressure are associated with elevated levels of interleukin-6 (IL-6) and intercellular adhesion molecule-1 [11] .…”

Section: Causes Of Inflammationmentioning

confidence: 99%

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

Dai

Gołembiewska

Lindholm

et al. 2017

Contributions to Nephrology

146

119

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Despite marked improvements in renal replacement therapy during the last 30 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients is still unacceptably high and comparable to that of many malignancies. Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in ESRD patients. However, traditional risk factors can only partially explain the high premature cardiovascular burden in this population. Nontraditional risk factors, including persistent low-grade inflammation, are critical in the pathogenesis of atherosclerosis, vascular calcification, and other causes of CVD and may also contribute to protein-energy wasting and other complications in chronic kidney disease (CKD) patients. Inflammatory biomarkers, such as high sensitivity C-reactive protein and interleukin-6, independently predict mortality in these patients. The causes of inflammation in CKD are multifactorial and include imbalance between increased production (due to multiple sources of inflammatory stimuli such as oxidative stress, acidosis, volume overload, co-morbidities, especially infections, genetic and epigenetic influences, and the dialysis procedure) and inadequate removal (due to decreased glomerular filtration rate or in ESRD patients, inadequate dialytic clearance) of pro-inflammatory cytokines. Though there are currently no established guidelines for the treatment of low-grade inflammation in ESRD patients, several strategies have been proposed, such as lifestyle modifications, pharmacological treatment, and optimization of dialysis. Further studies on pathways involved in pathogenic processes of inflammation in ESRD, and long-term effects of anti-inflammatory interventions targeting production or removal of cytokines or both on premature CVD and clinical outcomes in this patient group are warranted.

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“…Higher levels of both cytokines are associated with a higher risk of coronary heart disease (32) and have been implicated in the development of impaired kidney function (33,34) and diabetic retinopathy (35,36). Therefore, further analyses are planned to investigate whether IL-6 and TNF-a also predict these micro-and macrovascular complications in the KORA cohort and whether it will be possible to identify distinct biomarker profiles for the incidence of specific comorbidities and for their combined risk.…”

Section: Il-6 Tnf-a and Incident Dspnmentioning

confidence: 99%

Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study

et al. 2017

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OBJECTIVEExperimental and epidemiological studies have implicated inflammatory processes in the pathogenesis of distal sensorimotor polyneuropathy (DSPN), but prospective studies are lacking. We hypothesized that biomarkers of inflammation predict the development and progression of DSPN in a population-based cohort. RESEARCH DESIGN AND METHODSThis study was based on participants aged 62-81 years from the Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort, with a mean follow-up of 6.5 years. The predictive value of systemic levels of eight biomarkers of inflammation was assessed for incident DSPN in 133 incident case subjects and 397 individuals without incident DSPN, and for DSPN progression in 57 patients with prevalent DSPN at both time points. RESULTSHigher hs-CRP, interleukin (IL)-6, tumor necrosis factor (TNF)-a, IL-1 receptor antagonist (IL-1RA), and soluble intercellular adhesion molecule (sICAM-1) and lower adiponectin levels were associated with incident DSPN in age-and sexadjusted analysis; IL-18 and omentin were not. IL-6 (odds ratio 1.31 [95% CI 1.00-1.71]) and TNF-a (odds ratio 1.31 [95% CI 1.03-1.67]) remained associated with incident DSPN after adjusting for known DSPN risk factors. The addition of both cytokines to a clinical risk model improved model fit and reclassification. sICAM-1 and IL-1RA were positively associated with progression of DSPN. CONCLUSIONSSystemic subclinical and vascular inflammation predicted both the onset and progression of DSPN over 6.5 years in an older general population. Thus modulation of inflammatory processes may be relevant to prevent and/or treat diabetic neuropathy.Distal sensorimotor polyneuropathy (DSPN) is the most frequent neurological complication of type 2 diabetes (1). The pathomechanisms leading to the onset and progression of DSPN are not completely understood, which profoundly limits current prevention and treatment. Advanced age and diabetes duration represent the most important known risk factors, but there is increasing evidence that height,

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Inflammatory Cytokines in Diabetic Nephropathy

Cited by 219 publications

References 124 publications

Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-κB pathway

Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-κB pathway

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

Proinflammatory Cytokines Predict the Incidence and Progression of Distal Sensorimotor Polyneuropathy: KORA F4/FF4 Study

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