Evidence map›Paper›PMID 38414248›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024

Activation of the YAP/KLF5 transcriptional cascade in renal tubular cells aggravates kidney injury.

Yang Liu, Yu Wang, Chunhua Xu, Yu Zhang, Yang Wang, Jinzhong Qin, Hui-Yao Lan, Li Wang, Yu Huang, Kingston Kinglun Mak and 2 more

Open access · greenAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

10 citing papers in PubMed, 14 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

12 authors at 6 institutions in 2 countries.

Yang LiuSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Nephrology, Center of Nephrology and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Yu WangDepartment of Endocrinology and Metabolism, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China.
Chunhua XuShulan International Medical College, Zhejiang Shuren University, Hangzhou, China.
Yu ZhangDepartment of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, China.
Yang WangSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Jinzhong QinThe Key Laboratory of Model Animal for Disease Study of the Ministry of Education, Model Animal Research Center, Nanjing University, Nanjing, China.
Hui-Yao LanDepartment of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Guangdong-Hong Kong Joint Laboratory for Immune and Genetic Kidney Disease, The Chinese University of Hong Kong, Hong Kong, China.
Li WangDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
Yu HuangDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
Kingston Kinglun MakDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, China. Electronic address: kingston.mak@cityu.edu.hk.
Zhihua ZhengDepartment of Nephrology, Center of Nephrology and Urology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China. Electronic address: zhzhihua@mail.sysu.edu.cn.
Yin XiaSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Guangdong-Hong Kong Joint Laboratory for Immune and Genetic Kidney Disease, The Chinese University of Hong Kong, Hong Kong, China; Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. Electronic address: xia.yin@cuhk.edu.hk.
Chinese University of Hong Kong · HKCity University of Hong Kong · HKSun Yat-sen University · CNHarbin Medical University · CNModel Animal Research Center · CNZhejiang Shuren University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Hippo/YAP pathway plays a critical role in tissue homeostasis. Our previous work demonstrated that renal tubular YAP activation induced by double knockout (dKO) of the upstream Hippo kinases Mst1 and Mst2 promotes tubular injury and renal inflammation under basal conditions. However, the importance of tubular YAP activation remains to be established in injured kidneys in which many other injurious pathways are simultaneously activated. Here, we show that tubular YAP was already activated 6 h after unilateral ureteral obstruction (UUO). Tubular YAP deficiency greatly attenuated tubular cell overproliferation, tubular injury, and renal inflammation induced by UUO or cisplatin. YAP promoted the transcription of the transcription factor KLF5. Consistent with this, the elevated expression of KLF5 and its target genes in Mst1/2 dKO or UUO kidneys was blocked by ablation of Yap in tubular cells. Inhibition of KLF5 prevented tubular cell overproliferation, tubular injury, and renal inflammation in Mst1/2 dKO kidneys. Therefore, our results demonstrate that tubular YAP is a key player in kidney injury. YAP and KLF5 form a transcriptional cascade, where tubular YAP activation induced by kidney injury promotes KLF5 transcription. Activation of this cascade induces tubular cell overproliferation, tubular injury, and renal inflammation.

Indexed as

Adaptor Proteins, Signal TransducingKidney TubulesKruppel-Like Transcription FactorsYAP-Signaling ProteinsAnimalsCell Cycle ProteinsCell ProliferationCisplatinDisease Models, AnimalGene Expression RegulationHippo KinasesMiceMice, KnockoutPhosphoproteinsProtein Serine-Threonine KinasesSerine-Threonine Kinase 3Adaptor Proteins, Signal TransducingCell Cycle ProteinsCisplatinHippo KinasesKlf5 protein, mouseKruppel-Like Transcription FactorsPhosphoproteinsProtein Serine-Threonine KinasesSerine-Threonine Kinase 3Stk3 protein, mouseStk4 protein, mouseYap1 protein, mouseYAP-Signaling ProteinsHippokidneyKLF5MST1MST2tubular injuryUUOYAP

Identifiers

PMID38414248
PMCPMC11081877
OpenAlexW4392195713

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.