PXD021741

PXD021741 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	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:29:50.189.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021741
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	monohydroxylated residue; acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-29 05:27:00	ID requested
1	2023-03-10 16:16:27	announced
⏵ 2	2023-11-14 08:29:51	announced	2023-11-14: Updated project metadata.

10.6019/PXD021741;

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]

submitter keyword: Shotgun, murine,Fibroblast ablated, labelfree analysis

Suneel Apte
contact affiliation	Suneel Apte lab, Biomedical engineering department, Learner research institute Cleveland Clinic
contact email	aptes@ccf.org
lab head
Sumit Bhutada
contact affiliation	Cleveland Clinic
contact email	bhutads@ccf.org
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/2023/03/PXD021741

PRIDE project URI

• PRIDE
  1. PXD021741
     1. Label: PRIDE project
     2. Name: Consequences of fibroblast ablation in adult murine hearts