PXD042087

PXD042087 is an original dataset announced via ProteomeXchange.

Title	High-salt diet promotes hypertrophic scarring through TRPC3-mediated mitochondrial Ca2+ homeostasis dysfunction
Description	Diet High in salt content have been associated with cardiovascular disease and chronic inflammation. We recently demonstrated that transient receptor potential canonical 3 (TRPC3) channels regulate myofibroblast transdifferentiation in hypertrophic scars. Here, we examined how high salt activation of TRPC3 participates in hypertrophic scarring during wound healing. In vitro, we confirmed that high salt increased the TRPC3 protein expression and the marker of myofibroblast alpha smooth muscle actin (α-SMA) in wild-type mice (WT) primary cultured dermal fibroblasts but not Trpc3-/- mice. Activation of TRPC3 by high salt elevated cytosolic Ca2+ influx and mitochondrial Ca2+ uptake in dermal fibroblasts in a TRPC3-dependent manner. High salt activation of TRPC3 enhanced mitochondrial respiratory dysfunction and excessive reactive oxygen species (ROS) production by inhibiting pyruvate dehydrogenase action, that activated ROS-triggered Ca2+ influx and the Rho kinase/MLC pathway in WT mice but not Trpc3-/- mice. In vivo, a persistent high-salt diet promoted myofibroblast transdifferentiation and collagen deposition in a TRPC3-dependent manner. Therefore, this study demonstrates that high salt enhances myofibroblast transdifferentiation and promotes hypertrophic scar formation through enhanced mitochondrial Ca2+ homeostasis, which activates the ROS-mediated pMLC/pMYPT1 pathway. TRPC3 deficiency antagonizes high salt diet-induced hypertrophic scarring. TRPC3 may be a novel target for hypertrophic scarring during wound healing.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:10:29.874.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wejie Xia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-09 08:27:36	ID requested
1	2023-10-24 12:53:55	announced
⏵ 2	2023-11-14 09:10:31	announced	2023-11-14: Updated project metadata.

Xia W, Wang Q, Lin S, Wang Y, Zhang J, Wang H, Yang X, Hu Y, Liang H, Lu Y, Zhu Z, Liu D, homeostasis dysfunction. Heliyon, 9(8):e18629(2023) [pubmed]

submitter keyword: High salt;hypertrophic scar;TRPC3

Liu Daoyan
contact affiliation	Department of Wound Infection and Drug, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, P. R. China
contact email	liudaoyan@tmmu.edu.cn
lab head
Wejie Xia
contact affiliation	Department of Plastic & Cosmetic Surgery, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing 400042, P. R. China
contact email	xiaweijie@tmmu.edu.cn
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/2023/10/PXD042087

PRIDE project URI

• PRIDE
  1. PXD042087
     1. Label: PRIDE project
     2. Name: High-salt diet promotes hypertrophic scarring through TRPC3-mediated mitochondrial Ca2+ homeostasis dysfunction