Evidence map›Paper›PMID 38072665›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Discovery of PRDM16-Mediated TRPA1 Induction as the Mechanism for Low Tubulo-Interstitial Fibrosis in Diabetic Kidney Disease.

Fang Xu, Hongwei Jiang, Xiaozhou Li, Jian Pan, Huiling Li, Luxiang Wang, Pan Zhang, Junxiang Chen, Shuangfa Qiu, Yuxin Xie and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
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

21 citing papers in PubMed, 24 citations in OpenAlex.

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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

13 authors at 2 institutions in 2 countries.

Fang XuDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Hongwei JiangDepartment of Endocrinology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, 471000, P. R. China.
Xiaozhou LiDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Jian PanDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Huiling LiDepartment of Ophthalmology, Central South University, Changsha, Hunan, 410011, P. R. China.
Luxiang WangDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Pan ZhangDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Junxiang ChenDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Shuangfa QiuDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Yuxin XieDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Yijian LiDepartment of Urology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Dongshan ZhangDepartment of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.ORCID 0000-0002-7387-4804
Zheng DongDepartment of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, P. R. China.
Central South University · CNFirst Affiliated Hospital of Henan University of Science and Technology · CN

Funding

National Natural Science Foundation of China 82090024National Natural Science Foundation of China 82171088National Natural Science Foundation of China 82370703
6 · The paper itself

Abstract

The pathogenesis of Diabetic kidney disease(DKD) involves pathological changes in both tubulo-interstitium and the glomerulus. Surprisingly, tubulo-interstitial fibrosis (TIF), does not develop significantly until the late stage of DKD. Here, it is demonstrated that PR domain-containing 16 (PRDM16) is a key to the low level of TIF in DKD. In the experiments, PRDM16 is upregulated in high glucose-treated renal tubular cells, DKD mouse kidneys, and renal biopsy of human DKD patients via activation of NF-κB signal pathway. High glucose-induced expression of fibrotic proteins in renal tubular cells is suppressed by PRDM16. Mechanistically, PRDM16 bound to the promotor region of Transient receptor potential ankyrin 1 (TRPA1) to transactivate its expression and then suppressed MAPK (P38, ERK1/2) activation and downstream expression of TGF-β1. Knockout of PRDM16 from kidney proximal tubules in mice blocked TRPA1 expression and enhanced MAPK activation, TGF-β1 production, TIF development, and DKD progression, whereas knock-in of PRDM16 has opposite effects. In addition, overexpression of PRDM16 or its induction by formononetin ameliorated renal dysfunction and fibrosis in db/db diabetic mice. Finally, the above finding are detected in renal biopsies of DKD patients. Together, these results unveil PRDM16/TRPA1 as the mechanism responsible for the low level of TIF in the early stage of DKD by suppressing and TGF-β1 expression.

Indexed as

Diabetes Mellitus, ExperimentalDiabetic NephropathiesAnimalsDNA-Binding ProteinsFibrosisGlucoseHumansMiceMice, KnockoutTranscription FactorsTransforming Growth Factor beta1TRPA1 Cation ChannelDNA-Binding ProteinsGlucosePRDM16 protein, humanPrdm16 protein, mouseTranscription FactorsTransforming Growth Factor beta1TRPA1 Cation ChannelTRPA1 protein, humanTrpa1 protein, mousediabetic kidney diseaseMAPKPRDM16TGF-β1TRPA1tubulo-interstitial fibrosis

Identifiers

PMID38072665
PMCPMC10870028
OpenAlexW4389525746

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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 OpenQuestion graph.