Evidence mapPaperPMID 39205643Full record

ArticleActa biochimica et biophysica Sinica2024

Vaccarin suppresses diabetic nephropathy through inhibiting the EGFR/ERK1/2 signaling pathway.

Xuexue Zhu, Xinyu Meng, Xinyao Du, Chenyang Zhao, Xinyu Ma, Yuanyuan Wen, Shijie Zhang, Bao Hou, Weiwei Cai, Bin Du and 4 more

Abstract read
In one paragraph

Article in Acta biochimica et biophysica Sinica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Xuexue ZhuDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Xinyu MengDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Xinyao DuDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Chenyang ZhaoDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Xinyu MaDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Yuanyuan WenDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Shijie ZhangDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Bao HouDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Weiwei CaiDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Bin DuDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Zhijun HanDepartment of Clinical Research Center, Jiangnan University Medical Center, Wuxi 214001, China.
Fei XuDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Liying QiuDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Haijian SunDepartment of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diabetic nephropathy (DN) is recognized as one of the primary causes of chronic kidney disease and end-stage renal disease. Vaccarin (VAC) confers favorable effects on cardiovascular and metabolic diseases, including type 2 diabetes mellitus (T2DM). Nonetheless, the potential role and mechanism of VAC in the etiology of DN have yet to be completely elucidated. In this study, a classical mouse model of T2DM is experimentally induced via a high-fat diet (HFD)/streptozocin (STZ) regimen. Renal histological changes are assessed via H&E staining. Masson staining and immunohistochemistry (IHC) are employed to assess renal fibrosis. RT-PCR is utilized to quantify the mRNA levels of renal fibrosis, oxidative stress and inflammation markers. The levels of malondialdehyde (MDA) and reactive oxygen species (ROS), as well as the content of glutathione peroxidase (GSH-Px), are measured. The protein expressions of collagen I, TGF-β1, α-SMA, E-cadherin, Nrf2, catalase, SOD3, SOD2, SOD1, p-ERK, p-EGFR (Y845), p-EGFR (Y1173), p-NFκB P65, t-ERK, t-EGFR and t-NFκB P65 are detected by western blot analysis. Our results reveal that VAC has a beneficial effect on DN mice by improving renal function and mitigating histological damage. This is achieved through its inhibition of renal fibrosis, inflammatory cytokine overproduction, and ROS generation. Moreover, VAC treatment effectively suppresses the process of epithelial-mesenchymal transition (EMT), a crucial characteristic of renal fibrosis, in high glucose (HG)-induced HK-2 cells. Network pharmacology analysis and molecular docking identify epidermal growth factor receptor (EGFR) as a potential target for VAC. Amino acid site mutations reveal that Lys-879, Ile-918, and Ala-920 of EGFR may mediate the direct binding of VAC to EGFR. In support of these findings, VAC reduces the phosphorylation levels of both EGFR and its downstream mediator, extracellular signal-regulated kinase 1/2 (ERK1/2), in diabetic kidneys and HG-treated HK-2 cells. Notably, blocking either EGFR or ERK1/2 yields renal benefits similar to those observed with VAC treatment. Therefore, this study reveals that VAC attenuates renal damage via inactivation of the EGFR/ERK1/2 signaling axis in T2DM patients.

Indexed as

Diabetic NephropathiesErbB ReceptorsMAP Kinase Signaling SystemAnimalsDiabetes Mellitus, ExperimentalFibrosisHumansKidneyMaleMiceMice, Inbred C57BLMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Oxidative StressEGFR protein, mouseErbB ReceptorsMapk1 protein, mouseMapk3 protein, mouseMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3diabetic nephropathyEGFREMTrenal fibrosisvaccarin

Identifiers

PMID39205643
PMCPMC11972988

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.