PXD063137

PXD063137 is an original dataset announced via ProteomeXchange.

Title	Naringenin targets PI3K p85alpha to suppress PI3K/AKT signaling pathway and ameliorate disordered MMP-9 secretion in cigarette smoke extract-induced alveolar macrophages in vitro
Description	Naringenin has demonstrated potential therapeutic effects against cigarette smoke-induced lung injury; however, its underlying mechanisms of regulating matrix metalloproteinase-9 (MMP-9) in alveolar macrophages remain unclear. Methods: The regulatory mechanisms of naringenin in cigarette smoke extract (CSE)-induced alveolar macrophages were investigated using proteomics, and then naringenin’s targets were further validated by western blot, molecular docking, molecular dynamics (MD) simu-lations, cellular thermal shift assay (CETSA), and enzyme activity assay. Results: The proteomics revealed that the PI3K/AKT signaling pathway might play a crucial role in naringenin’s inhibition of MMP-9. Western blot confirmed that naringenin significantly inhibited CSE-upregulated PI3K/AKT signaling pathway and reduced MMP-9 expression in MH-S cells. Notably, the PI3K activator 740Y-P reversed naringenin’s effects on MMP-9. Additionally, molecular docking, MD simulations, and CETSA identified PI3K p85alpha as the potential binding site for naringenin, and naringenin markedly inhibited CSE-induced PI3K activity. In in vitro experiments, naringenin inhibiting MMP-9 secre-tion in alveolar macrophages contributed to alleviating elastin and E-cadherin damage in alveolar epithelial cells. Furthermore, naringenin effectively suppressed CSE-induced MMP-9 secretion in primary mouse alveolar macrophages and human THP-1-differentiated macrophages. Conclusions: Our findings revealed that naringenin, a potential candidate for treating smoking-induced lung injury, directly targeted PI3K p85alpha, inhibiting PI3K activity and MMP-9 expression in CSE-induced alveolar macrophages via suppressing the PI3K/AKT signaling pathway.
HostingRepository	iProX
AnnounceDate	2025-04-21
AnnouncementXML	Submission_2025-07-02_00:00:59.270.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Weiyang Fan
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-20 22:18:48	ID requested
1	2025-04-24 02:18:37	announced
⏵ 2	2025-07-02 00:01:00	announced	2025-07-02: Add info

Fan W, Xu Z, Zhong M, Wu X, Chen P, Chen Z, Su W, Wu H, Li P, Naringenin Targets PI3K p85alpha to Suppress PI3K/AKT Signaling Pathway and Ameliorate Disordered MMP-9 Secretion in Cigarette Smoke Extract-Induced Alveolar Macrophages In Vitro. Cells, 14(10):(2025) [pubmed]

submitter keyword: MH-S cells, LC-MSMS, alveolar macrophage, cigarette, naringenin

Peibo Li
contact affiliation	School of Life Sciences, Sun Yat-sen University
contact email	lipeibo@mail.sysu.edu.cn
lab head
Weiyang Fan
contact affiliation	School of Life Sciences, Sun Yat-sen University
contact email	2710053510@qq.com
dataset submitter

iProX dataset URI