PXD013635

PXD013635 is an original dataset announced via ProteomeXchange.

Title	Tendon tissue degradome in response to the patho-physiological niche
Description	Aberrant matrix turnover with elevated matrix proteolysis is a hallmark of tendon pathology. While tendon disease mechanisms remain obscure, mechanical cues are central regulators. Unloading of tendon explants in standard culture conditions provokes rapid cell-mediated tissue breakdown. Here we show that biological response to tissue unloading depends on the mimicked physiological context. Our experiments reveal that explanted tendon tissues remain functionally stable in a simulated avascular niche of low temperature and oxygen, regardless of the presence of serum. This hyperthermic and hyperoxic niche-dependent catabolic switch was shown by whole transcriptome analysis (RNA-seq) to be a strong pathological driver of an immune-modulatory phenotype, with a stress response to reactive oxygen species (ROS) and associated activation of catabolic extracellular matrix proteolysis that involved lysosomal activation and transcription of a range of proteolytic enzymes. Secretomic and degradomic analysis through terminal amine isotopic labeling of substrates (TAILS) confirmed that proteolytic activity in unloaded tissues was strongly niche dependent. Through targeted pharmacological inhibition we isolated ROS mediated oxidative stress as a major checkpoint for matrix proteolysis. We conclude from these data that the tendon stromal compartment responds to traumatic mechanical unloading in a manner that is highly dependent on the extrinsic niche, with oxidative stress response gating the proteolytic breakdown of the functional collagen backbone.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:56:12.272.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ulrich auf dem Keller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-25 06:09:06	ID requested
1	2020-01-28 02:05:27	announced
⏵ 2	2024-10-22 04:56:13	announced	2024-10-22: Updated project metadata.

Wunderli SL, Blache U, Beretta Piccoli A, Nieder, ö, st B, Holenstein CN, Passini FS, Silv, á, n U, Bundgaard L, Auf dem Keller U, Snedeker JG, Tendon response to matrix unloading is determined by the patho-physiological niche. Matrix Biol, 89():11-26(2020) [pubmed]

10.1016/j.matbio.2019.12.003;

curator keyword: Biological, Biomedical

submitter keyword: Mouse, Tendon, Thermo Q Exactive, TAILS

Ulrich auf dem Keller
contact affiliation	Technical University of Denmark
contact email	uadk@dtu.dk
lab head
Ulrich auf dem Keller
contact affiliation	Technical University of Denmark
contact email	ulrich.aufdemkeller@biol.ethz.ch
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/2020/01/PXD013635

PRIDE project URI

• PRIDE
  1. PXD013635
     1. Label: PRIDE project
     2. Name: Tendon tissue degradome in response to the patho-physiological niche