PXD067703-1

PXD067703 is an original dataset announced via ProteomeXchange.

Title	Mechanical compression reduces CC16 expression and disrupts metabolic homeostasis in airway epithelial cells
Description	Recent evidence suggests that bronchial epithelial cells from asthmatic patients exhibit altered metabolic signatures. This metabolic shift of energetically demanding cells leads to increased inflammation, excessive reactive oxygen species production (ROS), and oxidative stress—all hallmarks of mitochondrial dysfunction. While mitochondrial dysfunction has been implicated in asthmatic epithelial cells, the mechanistic link between bronchoconstriction and these metabolic alterations remains poorly defined. Club cell secretory protein (CC16) is the most abundant protein found in the lung and exerts key anti-inflammatory and antioxidant functions, culminating in protection against airway remodeling. Decreased levels of CC16 are characteristic of asthma and worsening respiratory disease. Using a well-established transmembrane compression system to model bronchoconstriction coupled with mass spectrometry and quantitative proteomics, we investigated how modeling bronchoconstriction in airway cells impacts CC16 expression and cell metabolic pathway changes over time. Additionally, using rCC16, we examined the direct impact on airway cell metabolism. Using naïve mouse tracheal epithelial cells (MTECs) and normal human bronchial epithelial cells (HBECs), we observed that rCC16 induces the expression of proteins related to various metabolic pathways, such as glycolysis, gluconeogenesis, and the pentose phosphate pathway and that compression of airway cells results in acute decreases in CC16 expression, as well as decreases in metabolic processes. MTECs deficient in CC16 (CC16-/-) had lower mitochondrial oxygen consumption rate (OCR) compared to WT cells, both of which could be increased by exogenous addition of rCC16. Our findings suggest a novel role for CC16 in mediating airway epithelial cell metabolic processes, which could be decreased by bronchoconstrictive events in asthma patients.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-24_17:19:48.569.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD067703
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Paul Langlais
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-25 10:00:57	ID requested
⏵ 1	2026-05-24 17:19:49	announced

10.6019/PXD067703;

10.1093/ajrcmb/aanag077;

Berthiaume Fox KA, Iannuzo N, Li J, Rojas-Quintero J, Kimura H, Santiago Raj PV, Schnellmann RG, Johnson MDL, Polverino F, Langlais PR, Kraft M, Park JA, Ledford JG, Mechanical compression reduces CC16 expression and disrupts metabolic homeostasis in airway epithelial cells. Am J Respir Cell Mol Biol, ():(2026) [pubmed]

submitter keyword: CC16, mitochondria,asthma

Julie Ledford
contact affiliation	Professor Cellular and Molecular Medicine Department University of Arizona College of Medicine - Tucson
contact email	jledford@arizona.edu
lab head
Paul Langlais
contact affiliation	University of Arizona
contact email	langlais@deptofmed.arizona.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/05/PXD067703

PRIDE project URI

• PRIDE
  1. PXD067703
     1. Label: PRIDE project
     2. Name: Mechanical compression reduces CC16 expression and disrupts metabolic homeostasis in airway epithelial cells