Evidence map›Paper›PMID 37891556›Full record

ArticleCardiovascular diabetology2023

Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease.

Wei Jiang, Chun Gan, Xindi Zhou, Qing Yang, Dan Chen, Han Xiao, Lujun Dai, Yaxi Chen, Mo Wang, Haiping Yang and 1 more

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

Article in Cardiovascular diabetology, 2023. 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
6.4field-weighted citation impact, top 3% 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, 32 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

11 authors at 4 institutions in 1 country.

Wei JiangChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Chun GanChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Xindi ZhouChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Qing YangChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Dan ChenChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Han XiaoChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Lujun DaiDepartment of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Yaxi ChenDepartment of Infectious Diseases, Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Mo WangChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Haiping YangChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China. oyhp0708@163.com.
Qiu LiChongqing Key Laboratory of Pediatrics, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, People's Republic of China. liqiu809@hospital.cqmu.edu.cn.
Children's Hospital of Chongqing Medical University · CNChongqing Medical University · CNChina International Science and Technology Cooperation · CNGuiyang Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveDiabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation.

methodsWe conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney.

resultsOur groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD.

conclusionOur findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD.

Indexed as

Diabetic NephropathiesKlotho ProteinsPodocytesAnimalsDiabetes MellitusGlucoseHumansKidneyLipoproteins, LDLMicerac1 GTP-Binding ProteinScavenger Receptors, Class ESignal TransductionGlucoseKlotho ProteinsLipoproteins, LDLOLR1 protein, humanoxidized low density lipoproteinrac1 GTP-Binding ProteinRAC1 protein, humanScavenger Receptors, Class EDKDIGF-1RKlothoox-LDL depositionPodocyte injuryRAC1

Identifiers

PMID37891556
PMCPMC10612302
OpenAlexW4387969789

What OpenQuestion 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 OpenQuestion graph.