EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress

Xu, Zheng; Zhao, Yunjie; Zhong, Peng; Wang, Jingying; Weng, Qiaoyou; Qian, Yuanyuan; Han, Jibo; Zou, Chunpeng; Liang, Guang

doi:10.18632/oncotarget.15948

Cited by 33 publications

(32 citation statements)

References 47 publications

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“…The primers used for gene expression quantification of pro-and antiinflammatory cytokines were: IL-6: Foward (F): 5′-TTCCATCCAGTTG CCTTCTTG-3′ and Reverse (R): 5′-AGGTCTGTTGGGAGTGGTATC-3′ (McGuire et al, 2016); IL-1β: F: 5′-CATCCAGCTTCAAATCTCGCAG-3′ and R: 5′-CACACACCAGCA GGTTATCATC-3′ (Liu et al, 2017); IL-10: F: 5′-CCCTTTGCTAT GGTGTCCTTTC-3′ and R: 5′-GATCTCCCTGGTTTCT CTTCCC-3′ (Darling, Toth, Arthur, & Clark, 2017); TGF-β: F: 5′-TGAC GTCACTGGAGTTGTACGG-3′ and R: 5′-GGTTC ATGTCATGGATGG TGC-3′ (Xu et al, 2017); TNF-α: F: 5′-CATCTTCTCAAAAT TCGAGTGA CAA-3′ and R: 5′-TGGGAGTAGACAAGGTACAACCC-3′ (Nikolaidis et al, 2010); GAPDH: F: 5′-AACTTTGGCATTGTGGAAGG-3′ and R: 5′-ACACATTGGGGGTAGGAACA-3′ (Liu, Guan & Ma, 2007). The conditions of the reaction were 50°C for two minutes, 95°C for 10 min and 40 repetitions of 95°C for 15 s and 60°C for one minute.…”

Section: Detection Of Cytokine Mrna Expressionmentioning

confidence: 99%

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

Marchesin

Celiberto

Orlando

et al. 2018

Journal of Functional Foods

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A B S T R A C TThis work investigates the effect of a soy-based probiotic drink (Enterococcus faecium CRL 183 and Bifidobacterium longum ATCC 15707) on the fecal microbiota composition, body weight and inflammatory parameters in diet-induced obese mice. The probiotic group had a lower body weight until 9th week of the study, reduced area and diameter of adipocytes, and showed a significant increase of IL-6 and IL-10 compared to the obesite non-treated group. The intake of a high-fat diet results in an increase of Lactobacillus spp. while the probiotic drink positively modulates the intestinal microbiota by maintaining the population of microorganisms belonging to the phylum Bacteroidetes and increases Bifidobacterium spp. Our study finds that the regular intake of this probiotic drink is able to reduce body weight gain and the size of adipocytes while modulating the fecal microbiota and the immune profile of animals, therefore acting in a beneficial manner in the control of obesity.

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Section: Detection Of Cytokine Mrna Expressionmentioning

confidence: 99%

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

Marchesin

Celiberto

Orlando

et al. 2018

Journal of Functional Foods

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“…Recent studies have painted an interesting picture on the emerging role of oxidative stress, whereby the excessive generation of ROS is associated with the structural and functional damage of various organs. Then, intracellular ROS generation has been reported to a potential mediator, which played an essential role in the induction of EMT and contributed to apoptosis in the progression of DN (Guo et al, ; Sun et al, ; Xu et al, ). Consistent with these studies, it has been confirmed in present study that high glucose conditions increased ROS generation.…”

Section: Discussionmentioning

confidence: 99%

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

Zhu

et al. 2019

Phytotherapy Research

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Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.

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“…Gain‐of‐function mutations in the EGFR gene are associated with a number of cancers . Recently, an increasing number of studies have linked EGFR activity with non‐cancerous chronic diseases, such as diabetic complications, atherosclerosis, renal fibrosis, obesity‐induced kidney diseases, and nonalcoholic fatty liver disease . In the retina, EGFR is highly expressed in several retinal cells, including retinal pigment epithelium (RPE) and Müller cells .…”

Section: Discussionmentioning

confidence: 99%

“…AG1478 significantly attenuated cardiac injury via inhibiting the phosphorylation of EGFR and Akt in the diabetic hearts . Another study also revealed that AG1478 inhibited EGFR and AKT activation, ameliorating ROS accumulation and ER stress and preventing diabetes‐induced renal injury . These findings suggest that blocking EGFR/Akt/ROS pathway may serve as a potential therapeutic strategy in preventing diabetic complications.…”

Section: Discussionmentioning

confidence: 99%

“…The AG1478 treatment was initiated after abnormal a‐waves and OPs amplitude were detected on week 10. Based on our previous studies, diabetic mice were orally treated with AG1478 (20 mg/kg) or vehicle (CMC‐Na, 200 μL) by gavage once daily from week 10 for 6 months (n = 8) . The corresponding control groups were treated with vehicle control (CMC‐Na, ig, intragastric injection administration, 200 μL) for the same duration (n = 8).…”

Section: Methodsmentioning

confidence: 99%

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EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

Yang

Yan

et al. 2018

Clin Exp Pharma Physio

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Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.

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EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress

Cited by 33 publications

References 47 publications

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

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