Evidence map›Paper›PMID 25262943›Full record

ArticleBritish journal of pharmacology2015

Pharmacological targeting of GSK3β confers protection against podocytopathy and proteinuria by desensitizing mitochondrial permeability transition.

Zhen Wang, Hui Bao, Yan Ge, Shougang Zhuang, Ai Peng, Rujun Gong

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

Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. GSK3β and the aging kidney.The Journal of clinical investigation · 2022
    Article
  9. Article
  10. Review
  11. Article
  12. The complicated role of mitochondria in the podocyte.American journal of physiology. Renal physiology · 2020
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. The Emerging Role of Mitochondrial Targeting in Kidney Disease.Handbook of experimental pharmacology · 2017
    Review
  20. Mitochondria Damage and Kidney Disease.Advances in experimental medicine and biology · 2017
    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

6 authors at 3 institutions in 2 countries.

Zhen WangDepartment of Nephrology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Division of Kidney Disease and Hypertension, Department of Medicine, Rhode Island Hospital, Brown University School of Medicine, Providence, RI, USA.
Hui Bao
Yan Ge
Shougang Zhuang
Ai Peng
Rujun Gong
Brown University · USRhode Island Hospital · USTongji University · CN

Funding

Therapeutic targeting of GSK3beta: A novel approach for podocyte protectionR01DK092485 · NIDDK · RHODE ISLAND HOSPITAL · PI GONG, RUJUN · 2011 to 2015
$1.8M
NIDDK NIH HHS R01 DK092485NIDDK NIH HHS R01DK092485
6 · The paper itself

Abstract

background and purposeMitochondrial dysfunction, triggered by mitochondria permeability transition (MPT), has been centrally implicated in the pathogenesis of podocytopathy and involves a multitude of cell signalling mechanisms, among which, glycogen synthase kinase (GSK) 3β has emerged as the integration point and plays a crucial role. This study aimed to examine the role of GSK3β in podocyte MPT and mitochondrial dysfunction. EXPERIMENTAL APPROACH: The regulatory effect of GSK3β on MPT was examined in differentiated podocytes in culture and in a murine model of adriamycin-induced podocytopathy using 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a highly selective small-molecule inhibitor of GSK3β. KEY

resultsTDZD-8 therapy prominently ameliorated the proteinuria and glomerular sclerosis in mice with adriamycin nephropathy; this was associated with a correction of GSK3β overactivity in the glomerulus and attenuation of podocyte injuries, including foot process effacement and podocyte death. Consistently, in adriamycin-injured podocytes, TDZD-8 treatment counteracted GSK3β overactivity, improved cell viability and prevented death, concomitant with diminished oxidative stress, improved mitochondrial dysfunction and desensitized MPT. Mechanistically, a discrete pool of GSK3β was found in podocyte mitochondria, which interacted with and phosphorylated clyclophilin F, a key structural component of the MPT pore. TDZD-8 treatment prevented the GSK3β-controlled phosphorylation and activation of cyclophilin F, desensitized MPT and alleviated the damage to mitochondria in podocytes induced by adriamycin in vivo and in vitro. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that pharmacological targeting of GSK3β could represent a promising and feasible therapeutic strategy for protecting podocytes against mitochondrial dysfunction induced by oxidative injuries.

Indexed as

AnimalsDisease Models, AnimalDoxorubicinGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMaleMiceMice, Inbred BALB CMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PorePermeabilityPodocytesProtein Kinase InhibitorsProteinuriaThiadiazoles4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dioneDoxorubicinGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, mouseMitochondrial Membrane Transport ProteinsMitochondrial Permeability Transition PoreProtein Kinase InhibitorsThiadiazoles

Identifiers

PMID25262943
PMCPMC4301697
OpenAlexW1542790326

What OpenQuestion 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 OpenQuestion graph.