Evidence map›Paper›PMID 37566086›Full record

ArticleCells2023

PAI-1 Regulation of p53 Expression and Senescence in Type II Alveolar Epithelial Cells.

Tapasi Rana, Chunsun Jiang, Sami Banerjee, Nengjun Yi, Jaroslaw W Zmijewski, Gang Liu, Rui-Ming Liu

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

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

22 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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

7 authors at 1 institution in 1 country.

Tapasi RanaDivision of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Chunsun JiangDivision of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Sami BanerjeeDivision of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.ORCID 0000-0002-6744-5763
Nengjun YiDepartment of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jaroslaw W ZmijewskiDivision of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Gang LiuDivision of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.ORCID 0000-0003-2615-131X
Rui-Ming LiuDivision of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
University of Alabama at Birmingham · US

Funding

Sex-dependent synergy between O3 exposure, APOE4 e4 genotype, and aging in the onset of Alzheimer's diseaseR01AG077395 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI RUI-MING LIU · 2023 to 2026
$1.8M
PAI-1 and aging-related susceptibility to lung fibrosisR56HL131054 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LIU, RUI-MING · 2016 to 2016
$438k
NHLBI NIH HHS R56 HL131054NIA NIH HHS R01 AG077395
6 · The paper itself

Abstract

Cellular senescence contributes importantly to aging and aging-related diseases, including idiopathic pulmonary fibrosis (IPF). Alveolar epithelial type II (ATII) cells are progenitors of alveolar epithelium, and ATII cell senescence is evident in IPF. Previous studies from this lab have shown that increased expression of plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor, promotes ATII cell senescence through inducing p53, a master cell cycle repressor, and activating p53-p21-pRb cell cycle repression pathway. In this study, we further show that PAI-1 binds to proteasome components and inhibits proteasome activity and p53 degradation in human lung epithelial A549 cells and primary mouse ATII cells. This is associated with a senescence phenotype of these cells, manifested as increased p53 and p21 expression, decreased phosphorylated retinoblastoma protein (pRb), and increased senescence-associated beta-galactose (SA-β-gal) activity. Moreover, we find that, although overexpression of wild-type PAI-1 (wtPAI-1) or a secretion-deficient, mature form of PAI-1 (sdPAI-1) alone induces ATII cell senescence (increases SA-β-gal activity), only wtPAI-1 induces p53, suggesting that the premature form of PAI-1 is required for the interaction with the proteasome. In summary, our data indicate that PAI-1 can bind to proteasome components and thus inhibit proteasome activity and p53 degradation in ATII cells. As p53 is a master cell cycle repressor and PAI-1 expression is increased in many senescent cells, the results from this study will have a significant impact not only on ATII cell senescence/lung fibrosis but also on the senescence of other types of cells in different diseases.

Indexed as

Alveolar Epithelial CellsIdiopathic Pulmonary FibrosisPlasminogen Activator Inhibitor 1Tumor Suppressor Protein p53AnimalsHumansMiceProteasome Endopeptidase ComplexPlasminogen Activator Inhibitor 1Proteasome Endopeptidase ComplexSERPINE1 protein, humanTP53 protein, humanTrp53 protein, mouseTumor Suppressor Protein p53ATII cell senescencep53 degradationPAI-1proteasome activity

Identifiers

PMID37566086
PMCPMC10417428
OpenAlexW4385607510

What OpenQuestion 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 OpenQuestion graph.