Evidence map›Paper›PMID 39134014›Full record

ArticleJournal of innate immunity2024

MDM2 Is Essential to Maintain the Homeostasis of Epithelial Cells by Targeting p53.

Su Wang, Shufen Zhong, Ying Huang, Songling Zhu, Shuangfeng Chen, Ran Wang, Sonam Wangmo, Bo Peng, Houkun Lv, Jichao Yang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of innate immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

15 authors.

Su WangDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Shufen ZhongState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Ying HuangState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Songling ZhuDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Shuangfeng ChenSchool of Life Science and Technology, Shanghai Tech University, Shanghai, China.
Ran WangDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Sonam WangmoSchool of Life Science and Technology, Shanghai Tech University, Shanghai, China.
Bo PengDepartment of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Houkun LvSchool of Life Science and Technology, Shanghai Tech University, Shanghai, China.
Jichao YangSchool of Life Science and Technology, Shanghai Tech University, Shanghai, China.
Liyan MaState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Zhiyang LingState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Yaguang ZhangMed-X Institute, Center for Immunological and Metabolic Diseases, The First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an Jiao Tong University, Xi'an, China.
Pengfei SuiState Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Bing SunDivision of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionMDM2 is known as the primary negative regulator of p53, and MDM2 promotes lung cancer fibrosis and lung injury through p53-dependent and p53-independent pathways. However, the mechanism by which MDM2 influences the pathogenesis of asthma is unknown. In this study, we investigated the function of MDM2 in lung epithelial cells in type 2 lung inflammation.

methodsWe used type II alveolar epithelial cell-specific heterozygous knockout of Mdm2 mice to validate its function. Then papain-induced asthma model was established, and changes in inflammation were observed by measuring immunohistochemistry and flow cytometry analysis.

resultsIn this study, we knockdown the mouse Mdm2 gene in type 2 alveolar epithelial cells. We demonstrated that heterozygous Mdm2 gene-deleted mice were highly susceptible to protease allergen papain-induced pulmonary inflammation characterized by increased ILC2 numbers, IL-5 and IL-13 cytokine levels, and lung pathology. A mechanistic study showed that following the decreased expression of Mdm2 in lung epithelial cells and A549 cell line, p53 was overactivated, and the expression of its downstream genes p21, Puma, and Noxa was elevated, which resulted in apoptosis. After Mdm2 knockdown, the mRNA expression of inflammation-related gene IL-25, HMGB1, and TNF-α were increased, which further amplified the downstream ILC2 response and lung inflammation.

conclusionThese results indicate that Mdm2 maintains the homeostasis of lung epithelial cells by targeting P53 and regulates the function of lung epithelial cells under type 2 lung inflammation.

Indexed as

AsthmaHomeostasisMice, KnockoutProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53A549 CellsAlveolar Epithelial CellsAnimalsApoptosisDisease Models, AnimalEpithelial CellsHumansMiceMice, Inbred C57BLPapainPneumoniaMdm2 protein, mousePapainProto-Oncogene Proteins c-mdm2Trp53 protein, mouseTumor Suppressor Protein p53Alveolar type 2 cellsApoptosisMDM2p53Type 2 lung inflammation

Identifiers

PMID39134014
PMCPMC11521410

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.