Inflammatory Targets in Diabetic Nephropathy

Donate-Correa, Javier; Luis-Rodríguez, Desirée; Martín‐Núñez, Ernesto; Tagua, Víctor G.; Hernández-Carballo, Carolina; Ferri, Carla; Rodríguez-Rodríguez, Ana Elena; Mora‐Fernández, Carmen; Navarro‐González, Juan F.

doi:10.3390/jcm9020458

Cited by 135 publications

(130 citation statements)

References 217 publications

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“…As shown in the GO enrichment analysis results, the potential targets of shenzhuo formula acting on DN were mainly associated with various biological processes, such as lipopolysaccharide-mediated signaling pathway, inflammatory response, positive regulation of cyclase activity, protein kinase B signaling, positive regulation of MAP kinase activity, response to estradiol, which have a strongly direct correlation with the pathogenesis of DN [28][29][30][31][32][33][34].…”

Section: Discussionmentioning

confidence: 95%

Network Pharmacology-based Prediction of Mechanism of Shenzhuo Formula for Application to DN

Wang

Han

Zhang

et al. 2020

Preprint

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Background: Shenzhuo formula is a traditional Chinese medicine (TCM) prescription which has significant therapeutic effects on diabetic nephropathy (DN). However, its mechanism remains unknown. Therefore, this study aimed to explore the underlying anti-DN mechanism of shenzhuo formula.Methods: The active ingredients and targets of shenzhuo formula were obtained by searching TCMSP, TCMID, SwissTargetPrediction and HIT. The DN target was identified from TTD, DrugBank and DisGeNet. The potential targets were obtained and PPI network were built after mapping the disease and drug targets. The key targets were screened out by network topology and the “drugs - DN - key targets” network was constructed by Cytoscape. GO analysis and KEGG pathway enrichment analysis were performed using DAVID, and the results were visualized using the Omicshare Tools.Results: We obtained 182 potential targets and 30 key targets. Ulteriorly, “drugs - DN - key targets” network were constructed, and results showed that nodes like M51, M21, M5, M71, M28, EGFR, MMP9, MAPK8, PIK3CA and STAT3 had a higher degree. GO analysis results mainly involved in positive regulation of transcription from RNA polymerase II promoter, inflammatory response, lipopolysaccharide-mediated signalingpathway and other biological processes. The results of KEGG showed that DN-related pathways like TNF signaling pathway, PI3K-Akt signaling pathway were at the top of the list.Conclusion: This article reveals the possible mechanism of shenzhuo formula in the treatment of DN through network pharmacology research, and lays a foundation for further studies.

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Section: Discussionmentioning

confidence: 95%

Network Pharmacology-based Prediction of Mechanism of Shenzhuo Formula for Application to DN

Wang

Han

Zhang

et al. 2020

Preprint

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“…In order to further explore the pathogenesis of DKD, our research group obtained a KEGG pathway map of miR-4534 through bioinformatics analysis ( Figure 8 ), of which SIRT1/FOXO signaling pathway ( 30 ) is most closely related to DKD. It is well-known that studies on the pathogenesis of DKD are increasingly focused on inflammatory responses ( 31 ), and FOXO is one of the most well-known pathways. Our research group has been working on the pathogenesis of DKD for a long time and has investigated the role of FOXO1 variant in DKD for the first time ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Urinary Exosomal MiRNA-4534 as a Novel Diagnostic Biomarker for Diabetic Kidney Disease

et al. 2020

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Urinary exosomal miRNAs can reflect the physiological and possibly pathophysiological state of cells lining the kidney and participate in the regulation of transcription and translation of proteins, which are playing an important role in the pathogenesis of diabetic kidney disease. In the present study, urine was collected from DM and DKD patients with a duration more than 10 years and urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from three patients with type 2 diabetes (DM) and three patients with type 2 diabetic kidney disease (DKD) using Exiqon's microRNA arrays. In total, the expression of 14 miRNAs (miR-4491, miR-2117, miR-4507, miR-5088-5P, miR-1587, miR-219a-3p, miR-5091, miR-498, miR-4687-3p, miR-516b-5p, miR-4534, miR-1275, miR-5007-3p, and miR-4516) was up-regulated (>2-fold) in DKD patients compared to healthy controls and DM patients. We used qRT-PCR based analysis of these 14 miRNAs in urinary exosomes from 14 DKD to 14 DM patients in confirmation cohort, among which seven miRNAs were consistent with the microarray results. The expressions of miR-4534 and miR-516b-5p correlated with trace proteinuria levels in the confirmation cohort. In conclusion, it has been confirmed that the expression of urinary exosomal miRNA in patients with type 2 diabetes DKD has changed. Mir-4534 might affect the FoxO signaling pathway by targeting BNIP3, and is expected to become a new biomarker for the progression of type 2 DKD disease, which will provide further research on the pathogenesis of DKD.

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“…[ 68 ] Many studies reported that the proinflammatory cytokines such as MCP1, ICAM1 and TGF‐β1 are elevated in diabetic kidneys and can thus contribute to diabetic nephropathy. [ 12,13 ] It translocates from the cytoplasm to the nucleus and induces the expression of MCP1, ICAM1 and TGF‐β1, leading to inflammation, glomerulosclerosis and tubulointerstitial fibrosis. [ 14 ] The present finding showed that treatment with BMFE caused downregulation of VCAM1, TNF‐α, fibronectin mRNA expression, explaining the protective effect of BMFE against DN through decreasing ROS and contributing to an increase in antioxidant activity in addition to and downregulation of gene expressions of VCAM1, TNF‐α and fibronectin that play a critical role in the glomerulosclerosis and tubulointerstitial fibrosis included in DN.…”

Section: Discussionmentioning

confidence: 99%

“…[ 11 ] Many studies reported that the proinflammatory cytokines such as monocyte chemoattractant proteins‐1 (MCP‐1), intercellular adhesion molecule‐1 (ICAM‐1) and transforming growth factors‐β‐1 (TGF‐β‐1) are elevated in diabetic kidneys leading to inflammation state, glomerulosclerosis and tubulointerstitial fibrosis. [ 12‐14 ]…”

Section: Introductionmentioning

confidence: 99%

Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway

Abouzed

Sadek

Ghazy

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Methods Diabetic male Wistar rats were injected with black mulberry fruit extract (BMFE) at doses of 150 and 300 mg/kg body weight. After 4 weeks, microalbuminuria was estimated in addition to serum concentrations of glucose, insulin, creatinine and albumin. Key findings The study revealed a significant amelioration of all the measured parameters in diabetic animals. In addition, MDA, lipid peroxide levels and catalase activity were also improved. The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE. Treated rats showed downregulation of TNF-α, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin mRNA expression. Conclusion The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α, VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats. Therefore, BMFE as dietary supplement could be a promising agent in improving diabetic nephropathy. Methods Chemicals Authentic anthocyanin samples of cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside for high-performance liquid chromatography (HPLC) analysis were purchased from Phytoplan company (Germany). Streptozotocin (STZ), chloroform and isopropanol were obtained from Sigma-Aldrich (St. Louis, MO, USA). Authentic samples for HPLC analysis of flavonoids rutin, quercetin, quercetrin, catechin, kaemferol, naringin and phenolic acids chlorogenic, gallic, caffeic, ellagic and cinnamic acids were purchased from Sigma-Aldrich, Germany and were kindly supplied by Food Technology Research Institute, Giza, Egypt. TRizol was obtained from Genetix Branid Co. (Genetix Biotech Asia Pvt. Ltd., New Delhi, India). QuantiFast SYBR Green PCR Master Mix unit was provided by QIAGEN (Hilden, Germany). HiSenScript TM [-] cDNA synthesis kit was purchased from iNtRON Biotechnology Company. The other reagents were of analytical, high-performance liquid chromatography (HPLC), or the best accessible pharmaceutical grades.

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Inflammatory Targets in Diabetic Nephropathy

Cited by 135 publications

References 217 publications

Network Pharmacology-based Prediction of Mechanism of Shenzhuo Formula for Application to DN

Network Pharmacology-based Prediction of Mechanism of Shenzhuo Formula for Application to DN

Urinary Exosomal MiRNA-4534 as a Novel Diagnostic Biomarker for Diabetic Kidney Disease

Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway

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