Evidence map›Paper›PMID 36290302›Full record

ArticleBiology2022

WDR73 Depletion Destabilizes PIP4K2C Activity and Impairs Focal Adhesion Formation in Galloway-Mowat Syndrome.

Hongyan Li, Fang Liu, Hanzhe Kuang, Hua Teng, Siyi Chen, Sijing Zeng, Qimin Zhou, Zhaokai Li, Desheng Liang, Zhuo Li and 1 more

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

Article in Biology, 2022. 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
0.7field-weighted citation impact, top 31% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. [Research progress on monogenic inherited glomerular diseases with central nervous system symptoms].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024
    Review
  3. Article
  4. Article
  5. Review
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

11 authors at 1 institution in 1 country.

Hongyan LiCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Fang LiuCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Hanzhe KuangCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Hua TengCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Siyi ChenCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Sijing ZengCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Qimin ZhouCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Zhaokai LiCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Desheng LiangCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.ORCID 0000-0002-9451-8585
Zhuo LiCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.ORCID 0000-0001-6010-6139
Lingqian WuCenter for Medical Genetics, Hunan Key Laboratory of Medical Genetics & Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha 410000, China.
Central South University · CN

Funding

National Natural Science Foundation of China 81974240, 81970829, 82171711the Key Grant of Research and Development in Hunan Province 2020DK2002the National Key R&D Program of China 2021YFC1005301, 2021YFC1005302the Science Technology Innovation Program of Hunan Province 2019SK1010, 2019SK1014
6 · The paper itself

Abstract

(1) Background: Galloway-Mowat syndrome (GAMOS) is a rare genetic disease, classically characterized by a combination of various neurological symptoms and nephrotic syndrome. WDR73 is the pathogenic gene responsible for GAMOS1. However, the pathological and molecular mechanisms of GAMOS1, especially nephrotic syndrome caused by WDR73 deficiency, remain unknown. (2) Methods and Results: In this study, we first observed remarkable cellular morphological changes including impaired cell adhesion, decreased pseudopodia, and G2/M phase arrest in WDR73 knockout (KO) HEK 293 cells. The differentially expressed genes in WDR73 KO cells were enriched in the focal adhesion (FA) pathway. Additionally, PIP4K2C, a phospholipid kinase also involved in the FA pathway, was subsequently validated to interact with WDR73 via protein microarray and GST pulldown. WDR73 regulates PIP4K2C protein stability through the autophagy-lysosomal pathway. The stability of PIP4K2C was significantly disrupted by WDR73 KO, leading to a remarkable reduction in PIP2 and thus weakening the FA formation. In addition, we found that podocyte-specific conditional knockout (Wdr73 CKO) mice showed high levels of albuminuria and podocyte foot process injury in the ADR-induced model. FA formation was impaired in primary podocytes derived from Wdr73 CKO mice. (3) Conclusions: Since FA has been well known for its critical roles in maintaining podocyte structures and function, our study indicated that nephrotic syndrome in GAMOS1 is associated with disruption of FA caused by WDR73 deficiency.

Indexed as

focal adhesionPIP2PIP4K2CWDR73

Identifiers

PMID36290302
PMCPMC9598763
OpenAlexW4297147734

What Socratic holds

Textmetadata
LicenceCC BY
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.