TNF-α pathway and T-cell immunity are activated early during the development of diabetic nephropathy in Type II Diabetes Mellitus

Lampropoulou, Ioanna; Stangou, Μaria; Sarafidis, Pantelis; Gouliovaki, Antigoni; Giamalis, Panagiotis; Tsouchnikas, Ioannis; Didangelos, Triantafyllos; Papagianni, Αikaterini

doi:10.1016/j.clim.2020.108423

Cited by 36 publications

(30 citation statements)

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“…Nonetheless, the immune system seems to be seriously affected, with oxidative and endoplasmic reticulum stress being major participants in the chronic inflammatory reactions of DM [24][25][26]. Both innate and adaptive immunity are affected; the diabetic milieu causes the activation of multiple signaling cascades, such as Janus kinase/signal transducer and activator of transcription (JAK-STAT), p38 mitogen-activated protein kinase (p38-MAPK) and TNF pathways, the increased expression of adhesion molecules, intracellular and extracellular receptors, and the production of proinflammatory cytokines (IL-1, IL-6, TNF-α, TGF-β), resulting in low-grade sustained inflammation [18,24,[27][28][29]. The influence of adaptive immunity has not been extensively studied in DM, although the activation of T and B cells has recently attracted interest [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

“…Both innate and adaptive immunity are affected; the diabetic milieu causes the activation of multiple signaling cascades, such as Janus kinase/signal transducer and activator of transcription (JAK-STAT), p38 mitogen-activated protein kinase (p38-MAPK) and TNF pathways, the increased expression of adhesion molecules, intracellular and extracellular receptors, and the production of proinflammatory cytokines (IL-1, IL-6, TNF-α, TGF-β), resulting in low-grade sustained inflammation [18,24,[27][28][29]. The influence of adaptive immunity has not been extensively studied in DM, although the activation of T and B cells has recently attracted interest [28][29][30]. Thus, the effect of IL17 on the progression of inflammation and proteinuria has been proven in experimental diabetic nephropathy, while regulatory T cells seem to have opposing effects by suppressing autoimmunity and ameliorating immune responses [31,32].…”

Section: Discussionmentioning

confidence: 99%

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CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Sampani

Daikidou

Lioulios

et al. 2021

IJMS

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Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Sampani

Daikidou

Lioulios

et al. 2021

IJMS

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“…The activation of the TNF signaling pathway can lead to glomerular vasoconstriction, a decrease of renal blood flow and glomerular filtration rate, and participation in the development of DN [ 33 ]. Moreover, TNF- α can cause inflammation of renal tissue, collagen deposition, and glomerular sclerosis, leading to kidney injury [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…TNF signal pathway, toll-like receptor signal pathway, MAPK signal pathway, and other signal pathways are important pathways of HGD on DN, which are mainly involved in inflammation, immunity, autophagy, and oxidative stress. e activation of the TNF signaling pathway can lead to glomerular vasoconstriction, a decrease of renal blood flow and glomerular filtration rate, and participation in the development of DN [33]. Moreover, TNF-α can cause inflammation of renal tissue, collagen deposition, and glomerular sclerosis, leading to kidney injury [34].…”

Section: Discussionmentioning

confidence: 99%

Based on Network Pharmacology and Molecular Docking to Explore the Underlying Mechanism of Huangqi Gegen Decoction for Treating Diabetic Nephropathy

Ding

Wang

Song

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Huangqi Gegen decoction (HGD), a Chinese herb formula, has been widely used to treat diabetic nephropathy in China, while the pharmacological mechanisms are still unclear. Therefore, the present study aims to explore the underlying mechanism of HGD for treating diabetic nephropathy (DN). Materials and Methods. Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), UniProt, and SwissTargetPrediction databases were used to search the active ingredients and potential targets of HGD. In addition, multiple disease-related databases were used to collect DN-related targets. Common targets of the protein-protein interaction (PPI) network were established using the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. At last, AutoDockVina was used to conduct molecular docking verification for the core components and targets. Results. A total of 27 active ingredients and 354 putative identified target genes were screened from HGD, of which 99 overlapped with the targets of DN and were considered potential therapeutic targets. Further analysis showed that the HGD activity of quercetin, formononetin, kaempferol, isorhamnetin, and beta-sitosterol ingredients is possible through VEGFA, IL6, TNF, AKT1, and TP53 targets involved in TNF, toll-like receptors, and MAPK-related pathways, which have anti-inflammatory, antiapoptosis, antioxidation, and autophagy effects, relieve renal fibrosis and renal cortex injury, and improve renal function, thus delaying the development of DN. The molecular docking results showed that quercetin, formononetin, kaempferol, isorhamnetin, beta-sitosterol had a good binding activity with VEGFA, IL6, TNF, AKT1, and TP53. Conclusion. This study demonstrated that HGD might take part in the treatment of DN through multicomponent, multitarget, and multichannel combined action.

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“…Studies have shown that aberrant intrarenal infiltration and activation of T cells are involved in the pathogenesis of DN in both clinical samples and streptozotocin (STZ)-induced diabetes mice ( Moon et al, 2012 ). Clinical findings show that T cell immunity and TNF-α signaling pathway are activated during the early development of DN in patients ( Moon et al, 2012 ; Lampropoulou et al, 2020 ). The proportions of T helper cells (Th1, Th2, Th17 and regulatory T (Treg) cells) in DN are altered with the increased levels of Th1 and Th17, and the decreased level of Treg ( Zhang et al, 2014 ).…”

Section: Inflammation In the Progression Of Dnmentioning

confidence: 99%

Epigenetics and Inflammation in Diabetic Nephropathy

Shao

Zhang

et al. 2021

Front. Physiol.

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Diabetic nephropathy (DN) leads to high morbidity and disability. Inflammation plays a critical role in the pathogenesis of DN, which involves renal cells and immune cells, the microenvironment, as well as extrinsic factors, such as hyperglycemia, chemokines, cytokines, and growth factors. Epigenetic modifications usually regulate gene expression via DNA methylation, histone modification, and non-coding RNAs without altering the DNA sequence. During the past years, numerous studies have been published to reveal the mechanisms of epigenetic modifications that regulate inflammation in DN. This review aimed to summarize the latest evidence on the interplay of epigenetics and inflammation in DN, and highlight the potential targets for treatment and diagnosis of DN.

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TNF-α pathway and T-cell immunity are activated early during the development of diabetic nephropathy in Type II Diabetes Mellitus

Cited by 36 publications

References 30 publications

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus

Based on Network Pharmacology and Molecular Docking to Explore the Underlying Mechanism of Huangqi Gegen Decoction for Treating Diabetic Nephropathy

Epigenetics and Inflammation in Diabetic Nephropathy

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