PXD011742

PXD011742 is an original dataset announced via ProteomeXchange.

Title	Mechanism of 17-β Estradiol Stimulated Integration of Human Mesenchymal Stem Cells in Heart Tissue
Description	Scarcity of gender specific donor hearts highlights the importance of mesenchymal stem cells (MSCs) as a therapeutic tool for heart repair. However, inefficient incorporation, retention, and activity of MSCs in cardiac tissue remains an obstacle. Since surge in follicular estradiol (μmolar-range) triggers tissue remodeling (e.g. ovulation) and estradiol exerts beneficial actions on the cardiovascular system, we hypothesized that estradiol may promote/improve MSC-mediated cardiac repair processes. Methods: Wharton’s jelly-derived MSCs were used, to assess the effects of estradiol on their proliferation, directed-migration and engraftment in murine heart slices, ex vivo. Results: MSCs expressed estrogen receptors (ERs) α and β, and estradiol promoted MSC proliferation (measured using xCELLigence real-time cell-impedance system and DNA-quantification). Estradiol up-regulated mRNA (qRT-PCR) and protein expression (western blotting) of ERα, ERβ, EMMPRIN, and MMP-9, yet down-regulated MMP-2 expression. In MSCs estradiol, up-regulated mRNA expression of VEGF-A, VCAM-1, and angiogenin, and stimulated NO production via ER. Proteomic analysis revealed that in MSCs estradiol up-regulated 47 proteins, down-regulated 7 proteins, and increased the expression of key biochemical components/pathways involved in tissue repair. In MSCs co-cultured with murine heart-slices, estradiol significantly induced MSC migration in an ER-dependent fashion (and preferentially via ERα) and significantly increased the secretion of MMP-2, MMP-9, angiogenin and VEGF. Conclusion: Estradiol facilitates the integration/engraftment of MSCs into heart slices by promoting MSC proliferation and migration and these beneficial effects are mediated via increases in molecules/pathways involved in tissue remodeling and angiogenesis. Priming of MSCs with estradiol may enhance their ability to repair/regenerate cardiac tissue in women.
HostingRepository	PRIDE
AnnounceDate	2019-06-24
AnnouncementXML	Submission_2019-06-24_03:09:49.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD011742
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Felicia Antohe
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	residues isobaric at 128.058578 Da; Oxidation; Carbamidomethyl
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-11-19 08:28:51	ID requested
⏵ 1	2019-06-24 03:09:51	announced

Mihai MC, Popa MA, Suica VI, Antohe F, Jackson EK, Simionescu M, Dubey RK, -estradiol stimulated integration of human mesenchymal stem cells in heart tissue. J Mol Cell Cardiol, 133():115-124(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: Estrogen, stem cells, heart disease, tissue remodeling, gender, women, heart repair

Felicia Antohe
contact affiliation	Proteomics Department, Institute of Cellular Biology and Pathology "N. Simionescu", Bucharest, Romania
contact email	felicia.antohe@icbp.ro
lab head
Felicia Antohe
contact affiliation	Institute of Cellular Biology and Pathology "N. Simionescu"
contact email	felicia.antohe@icbp.ro
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD011742
     1. Label: PRIDE project
     2. Name: Mechanism of 17-β Estradiol Stimulated Integration of Human Mesenchymal Stem Cells in Heart Tissue