Evidence mapPaperPMID 37230975Full record

ArticleNature communications2023

HDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice.

Yang Zhang, Yujie Yang, Fan Yang, Xiaohan Liu, Ping Zhan, Jichao Wu, Xiaojie Wang, Ziying Wang, Wei Tang, Yu Sun and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
14.5field-weighted citation impact, top 1% 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

54 citing papers in PubMed, 73 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

16 authors at 4 institutions in 1 country.

Yang ZhangThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.ORCID 0009-0002-1463-7064
Yujie YangThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Fan YangDepartment of Neurosurgery, Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Xiaohan LiuThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Ping ZhanThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Jichao WuThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Xiaojie WangThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Ziying WangThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Wei TangThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.ORCID 0000-0002-4573-3502
Yu SunThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Yan ZhangThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.ORCID 0000-0003-2219-5550
Qianqian XuDepartment of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, 250012, China.
Jin ShangDepartment of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Junhui ZhenDepartment of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.
Min LiuThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China. liuweimin@sdu.edu.cn.ORCID 0000-0001-5433-0302
Fan YiThe Key Laboratory of Infection and Immunity of Shandong Province, Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, China. fanyi@sdu.edu.cn.ORCID 0000-0001-8634-9788
Shandong University · CNFirst Affiliated Hospital of Zhengzhou University · CNQilu Hospital of Shandong University · CNShandong Provincial Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Renal tubular epithelial cells (TECs) play a key role in kidney fibrosis by mediating cycle arrest at G2/M. However, the key HDAC isoforms and the underlying mechanism that are involved in G2/M arrest of TECs remain unclear. Here, we find that Hdac9 expression is significantly induced in the mouse fibrotic kidneys, especially in proximal tubules, induced by aristolochic acid nephropathy (AAN) or unilateral ureter obstruction (UUO). Tubule-specific deletion of HDAC9 or pharmacological inhibition by TMP195 attenuates epithelial cell cycle arrest in G2/M, then reduces production of profibrotic cytokine and alleviates tubulointerstitial fibrosis in male mice. In vitro, knockdown or inhibition of HDAC9 alleviates the loss of epithelial phenotype in TECs and attenuates fibroblasts activation through inhibiting epithelial cell cycle arrest in G2/M. Mechanistically, HDAC9 deacetylates STAT1 and promotes its reactivation, followed by inducing G2/M arrest of TECs, finally leading to tubulointerstitial fibrosis. Collectively, our studies indicate that HDAC9 may be an attractive therapeutic target for kidney fibrosis.

Indexed as

Kidney DiseasesUreteral ObstructionAnimalsApoptosisCell Cycle CheckpointsCell Line, TumorEpithelial CellsFibrosisG2 Phase Cell Cycle CheckpointsHistone DeacetylasesKidneyKidney Tubules, ProximalMaleMiceRepressor ProteinsHdac9 protein, mouseHistone DeacetylasesRepressor Proteins

Identifiers

PMID37230975
PMCPMC10212923
OpenAlexW4378192683

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.