PXD021739-1

PXD021739 is an original dataset announced via ProteomeXchange.

Title	Consequences of fibroblast ablation in adult murine hearts
Description	Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. However, the in vivo role of fibroblasts in structuring the basal ECM network is poorly understood. To examine the effects of fibroblast loss on the microenvironment in the adult murine heart, we generated mice with reduced fibroblast numbers and evaluated the tissue microenvironment during homeostasis and after injury. We determined that a 60-80% reduction in fibroblasts numbers did not overtly change the fibrillar collagen network but did alter the distribution and abundance of type VI collagen, a microfibrillar collagen that forms an open network with the basement membrane. In fibroblast ablated mice, myocardial infarction did not result in ventricular wall rupture, and heart function was more effectively preserved during angiotensin II/phenylephrine (AngII/PE) induced fibrosis. Analysis of cardiomyocyte contractility demonstrated weaker contractions and slower calcium release and reuptake in uninjured and AngII/PE infused fibroblast ablated animals. Moreover, fibroblast ablated hearts have a similar gene expression prolife to hearts with exercise-induced and physiological hypertrophy after AngII/PE infusion. These results suggest that hearts are resilient to a significant degree of fibroblast loss and that fibroblasts can directly impact cardiomyocyte function. Furthermore, a reduction in fibroblasts may have cardioprotective effects heart after injury suggesting that manipulation of the number of fibroblasts may have therapeutic value.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_13:35:40.153.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021739
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sumit Bhutada
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	(R)-5-oxo-1,4-tetrahydrothiazine-3-carboxylic acid; iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; acetylated residue; deamidated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-29 05:26:28	ID requested
⏵ 1	2024-10-07 13:35:41	announced

Kuwabara JT, Hara A, Bhutada S, Gojanovich GS, Chen J, Hokutan K, Shettigar V, Lee AY, DeAngelo LP, Heckl JR, Jahansooz JR, Tacdol DK, Ziolo MT, Apte SS, Tallquist MD, fibroblast reduction in adult murine hearts. Elife, 11():(2022) [pubmed]

10.7554/elife.69854;

10.6019/PXD021739;

submitter keyword: Fibroblast Ablated, TAILS, Hearts,Murine, N-terminomics

Suneel Apte
contact affiliation	Cleveland Clinic
contact email	aptes@ccf.org
lab head
Sumit Bhutada
contact affiliation	Cleveland Clinic
contact email	bhutads@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021739
     1. Label: PRIDE project
     2. Name: Consequences of fibroblast ablation in adult murine hearts