Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways

Malik, Salma; Suchal, Kapil; Khan, Sana Irfan; Bhatia, Jagriti; Kishore, Kamal; Dinda, Amit Kumar; Arya, Dharamvir Singh

doi:10.1152/ajprenal.00393.2016

Cited by 204 publications

(127 citation statements)

References 52 publications

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“…Some of these pathways have been reported in various experimental diabetes models. MAPK-signaling plays crucial roles in DN because it is related to inflammatory, oxidative, and apoptotic processes [32]; evidence of its activation has been demonstrated on the kidney biopsies of diabetic patients [33]. High glucose levels are known to induce Ras/Rac1-dependent superoxide formation in rat mesangial cells [34,35].…”

Section: Discussionmentioning

confidence: 99%

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

Lee

et al. 2020

JCM

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Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabetes models and in patients with both diabetes and CKD. Here, we aimed to investigate pathologic miRs in diabetic nephropathy (DN) by prospectively following six nephrotic, biopsy-proven isolated DN patients (enrolled between August 2015 and July 2017) for one year. The urinary exosomes were isolated at the time of the biopsy and the contained miRs were analyzed by next-generation sequencing. The results were compared to the control group, composed of age-, gender-, and CKD stage-matched patients with proteinuric CKD who did not present diabetes. Among the 72 identified miRs, we investigated eight (miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c) exhibiting the strongest upregulation (13-15 fold) and two (miR-133a-3p and miR-153-3p) with the strongest downregulation (7-9 fold). The functional analysis of these miRs showed that they were involved in known and novel pathways of DN, supporting their pathologic roles. The bioinformatics-based prediction of the target genes of these miRs will inspire future research on the mechanisms underlying DN pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

Lee

et al. 2020

JCM

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“…Supporting evidence has come from recent research that TNF‐α and MAPK signaling pathways are involved in the pathogenesis of diabetes . DM‐induced cardiac dysfunction is reportedly associated with the activation of P38 MAPK .…”

Section: Discussionmentioning

confidence: 99%

Deep sea minerals ameliorate diabetic‐induced inflammation via inhibition of TNFα signaling pathways

Day

et al. 2019

Environmental Toxicology

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It has been well‐documented that the consumption of deep sea water (DSW) has beneficial effects on myocardial hypertrophy and cardiac apoptosis induced by hypercholesterolemia. However, the molecular mechanisms for the anti‐inflammatory effects of DSW on diabetic cardiomyopathy are still largely unclear. The main purpose of this present study was to test the hypothesis that DSW exerts anti‐inflammatory effects through the suppression of the TNF‐α‐mediated signaling pathways. IP injection of streptozotocin (STZ) at the dose of 65 mg/kg was used to establish a diabetes rat model. DSW mineral extracts that diluted in desalinated water were prepared in three different dosages and administered to the rats through gavages for 4 weeks. These dosages are DSW‐1X (equivalent to 37 mg Mg2+/kg/day), 2X (equivalent to 74 mg Mg2+/kg/day) and 3X (equivalent to 111 mg Mg2+ mg/kg/day). Immunofluorescence staining and Western blot showed that the protein expression level of TNF‐α was markedly higher in the STZ‐induced diabetic rat hearts than in the control group. Consequently, the phosphorylation levels of the TNF‐α‐modulated downstream signaling molecules and P38 mitogen‐activated protein kinases (MAPKs) were notably elevated in heart tissues of STZ‐induced diabetes. These higher phosphorylation levels subsequently upregulated NF‐κB‐modulated inflammatory mediators, such as cyclooxygenase (COX)‐II and inducible nitric oxide synthase (iNOS). However, treatment with DSW as well as MgSO4, the main mineral in DSW, significantly reversed all the alterations. These findings suggest that DSW has potential as a therapeutic agent for preventing diabetes‐related cardiovascular diseases.

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“…Both of these chemokines play a vital role in early inflammation. Acting as an important inflammatory signaling pathway, NF-κB mediates the pathogenesis and prognosis of DN [18][19][20]. In addition, the NF-κB p65 subunit is upregulated in circulating monocytes, renal tubular epithelium of diabetic patients, and mouse aortic endothelial cells [21,22].…”

Section: Discussionmentioning

confidence: 99%

Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism

Deng

Fan

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diabetic nephropathy is the one of the most serious microvascular complications of diabetes mellitus, and “metabolic memory” plays a vital role in the development of diabetic complications. To investigate the effect of epigenetics on metabolic memory, we analyzed the impact of transient high-glucose stimulation on the secretion of inflammatory factors from rat glomerular mesangial cells. Methods: Rat glomerular mesangial cells (HBZY-1) were divided into three groups: high-glucose group (25 mM glucose), hypertonic group (5.5 mM glucose+19.5 mM mannitol), and normal-glucose control group (5.5 mM glucose). Mesangial cells were cultured in high-glucose, hypertonic, and normal-glucose media for 24 h and transitioned to normal-glucose culture for 24, 48, and 72 h. Then, protein, mRNA, and supernatants were harvested. The expression of monomethylated H3K4 was determined by western blot analysis, and the expression of the NF-κB subunit p65 and histone methyltransferase set7/9 was determined by quantitative real-time PCR. The expression of monocyte chemoattractant protein 1 (MCP-1) and vascular cell adhesion molecule 1 (VCAM-1) was detected by an enzyme-linked immunosorbent assay. Results: Compared with the control group, H3K4me1 expression was upregulated after transient high-glucose stimulation, gradually downregulated in the following 48 h (P < 0.05), and reached the level of the control group at 72 h (P > 0.05). The expression of set7/9 was increased after 24 h of high-glucose stimulation and the following 24 h and 48 h (P < 0.05); it then returned to the level of the control group at 72 h. Compared with the control group, the increased expression of p65, VCAM-1, and MCP-1 was sustained for at least 72 h in the high-glucose group. Conclusion: Transient high-glucose stimulation can induce the persistent secretion of inflammatory factors from rat glomerular mesangial cells via histone modification.

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Apigenin ameliorates streptozotocin-induced diabetic nephropathy in rats via MAPK-NF-κB-TNF-α and TGF-β1-MAPK-fibronectin pathways

Cited by 204 publications

References 52 publications

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy

Deep sea minerals ameliorate diabetic‐induced inflammation via inhibition of TNFα signaling pathways

Transient High-Glucose Stimulation Induces Persistent Inflammatory Factor Secretion from Rat Glomerular Mesangial Cells via an Epigenetic Mechanism

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