Evidence map›Paper›PMID 25832774›Full record

ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2015

Enhanced epithelial-to-mesenchymal transition associated with lysosome dysfunction in podocytes: role of p62/Sequestosome 1 as a signaling hub.

Guangbi Li, Cai-Xia Li, Min Xia, Joseph K Ritter, Todd W B Gehr, Krishna Boini, Pin-Lan Li

Open access · goldAbstract read
In one paragraph

Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

39 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Applications and Mechanisms of TripterygiumFrontiers in pharmacology · 2022
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Podocyte Sphingolipid Signaling in Nephrotic Syndrome.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2021
    Review
  14. Article
  15. Article
  16. Lysosomal TRPML1 Channel: Implications in Cardiovascular and Kidney Diseases.Advances in experimental medicine and biology · 2021
    Article
  17. EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration.International journal of molecular sciences · 2020
    Review
  18. Article
  19. Article
  20. Article
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

7 authors at 1 institution in 1 country.

Guangbi LiDepartment of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Cai-Xia Li
Min Xia
Joseph K Ritter
Todd W B Gehr
Krishna Boini
Pin-Lan Li
Virginia Commonwealth University · US

Funding

Regulation of Lysosomes in Autophagy in Coronary Arterial MyocytesR01HL057244 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2001 to 2021
$6.7M
Subendothelial Exosomes in Coronary Microvascular DysfunctionR01HL075316 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2004 to 2024
$6.7M
Hypertension and glomerular injury in hyperhomocysteinemia - role of inflammatory exosomesR01DK054927 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 1998 to 2023
$6.7M
Lysosome dysfunction in podocytopathy and associated hypertensionR01DK120491 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI LI, PINLAN · 2018 to 2022
$2.4M
Instigation of Glomerular Injury by Inflammasomes in Obesity: Beyond InflammationR01DK104031 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI BOINI, KRISHNA M · 2015 to 2019
$1.7M
MECHANISM OF CORONARY ENDOTHELIUM MEDIATED VASODILATIONR29HL057244 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI LI, PIN-LAN · 1997 to 2000
$101k
NHLBI NIH HHS HL57244NHLBI NIH HHS HL75316NHLBI NIH HHS R01 HL057244NHLBI NIH HHS R01 HL075316NHLBI NIH HHS R29 HL057244NIDDK NIH HHS DK54927NIDDK NIH HHS R01 DK054927NIDDK NIH HHS R01 DK104031NIDDK NIH HHS R01 DK120491
6 · The paper itself

Abstract

backgroundAutophagy is of importance in the regulation of cell differentiation and senescence in podocytes. It is possible that derangement of autophagy under different pathological conditions activates or enhances Epithelial-to-Mesenchymal Transition (EMT) in podocytes, resulting in glomerular sclerosis. To test this hypothesis, the present study produced lysosome dysfunction by inhibition of the vacuolar H(+)-ATPase (V-ATPase) to test whether deficiency of autophagic flux leads to enhancement of EMT in podocytes. METHODS AND

resultsBy Western blot and confocal analysis, lysosome inhibition using a V-ATPase inhibitor or its siRNA was found to markedly decreases the epithelial markers (P-cadherin and ZO-1) and increases the mesenchymal markers (FSP-1 and α-SMA). This enhancement was accompanied by deficient autophagic flux, as demonstrated by marked increases in LC3B-II and p62/Sequestosome 1. However, inhibition of autophagosome formation using spaudin-1 significantly attenuated both enhancement of EMT and deficiency of autophagic flux. To explore the mechanisms by which deficient autophagic flux enhances EMT, we tested the role of accumulated p62 as a signal hub in this process. Neither the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear kappa-light-chain-enhancer pathways of p62 contributed to enhanced EMT. However, inhibition of cyclin-dependent kinase 1 (CDK1) activity reduced the phosphorylation of p62 and enhanced EMT in podocytes similar to lysosome dysfunction.

conclusionThe lack of phosphorylated p62 leads to a faster exit from cell mitosis, enhanced EMT associated with lysosome dysfunction may be attributed to accumulation of p62 and associated reduction of p62 phosphorylation.

Indexed as

ActinsAdaptor Proteins, Signal TransducingCadherinsCDC2 Protein KinaseCell DifferentiationCell LineEpithelial-Mesenchymal TransitionHumansLysosomesMacrolidesMicroscopy, ConfocalMitosisNF-E2-Related Factor 2NF-kappa BPodocytesRNA InterferenceACTA2 protein, humanActinsAdaptor Proteins, Signal Transducingbafilomycin ACadherinsCDC2 Protein KinaseMacrolidesNFE2L2 protein, humanNF-E2-Related Factor 2NF-kappa BRNA, Small InterferingSequestosome-1 ProteinSQSTM1 protein, humanTJP1 protein, humanVacuolar Proton-Translocating ATPasesZonula Occludens-1 Protein

Identifiers

PMID25832774
PMCPMC4391077
OpenAlexW1585035603

What OpenQuestion holds

Textmetadata
LicenceTDM
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.