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https://observatorio.fm.usp.br/handle/OPI/31902
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DC Field | Value | Language |
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dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | |
dc.contributor.author | ICLI, Basak | |
dc.contributor.author | WU, Winona | |
dc.contributor.author | OZDEMIR, Denizhan | |
dc.contributor.author | LI, Hao | |
dc.contributor.author | HAEMMIG, Stefan | |
dc.contributor.author | LIU, Xin | |
dc.contributor.author | GIATSIDIS, Giorgio | |
dc.contributor.author | CHENG, Henry S. | |
dc.contributor.author | AVCI, Seyma Nazli | |
dc.contributor.author | KURT, Merve | |
dc.contributor.author | LEE, Nathan | |
dc.contributor.author | GUIMARAES, Raphael Boesche | |
dc.contributor.author | MANICA, Andre | |
dc.contributor.author | MARCHINI, Julio F. | |
dc.contributor.author | RYNNING, Stein Erik | |
dc.contributor.author | RISNES, Ivar | |
dc.contributor.author | HOLLAN, Ivana | |
dc.contributor.author | CROCE, Kevin | |
dc.contributor.author | ORGILL, Dennis P. | |
dc.contributor.author | FEINBERG, Mark W. | |
dc.date.accessioned | 2019-05-30T13:45:15Z | |
dc.date.available | 2019-05-30T13:45:15Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | FASEB JOURNAL, v.33, n.4, p.5599-5614, 2019 | |
dc.identifier.issn | 0892-6638 | |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/31902 | |
dc.description.abstract | Angiogenesis is a critical process in repair of tissue injury that is regulated by a delicate balance between pro- and antiangiogenic factors. In disease states associated with impaired angiogenesis, we identified that miR-135a-3p is rapidly induced and serves as an antiangiogenic microRNA (miRNA) by targeting endothelial cell (EC) p38 signaling in vitro and in vivo. MiR-135a-3p overexpression significantly inhibited EC proliferation, migration, and network tube formation in matrigel, whereas miR-135-3p neutralization had the opposite effects. Mechanistic studies using transcriptomic profiling, bioinformatics, 3'-UTR reporter and miRNA ribonucleoprotein complex -immunoprecipitation assays, and small interfering RNA dependency studies revealed that miR-135a-3p inhibits the p38 signaling pathway in ECs by targeting huntingtin-interacting protein 1 (HIP1). Local delivery of miR-135a-3p inhibitors to wounds of diabetic db/db mice markedly increased angiogenesis, granulation tissue thickness, and wound closure rates, whereas local delivery of miR-135a-3p mimics impaired these effects. Finally, through gain- and loss-of-function studies in human skin organoids as a model of tissue injury, we demonstrated that miR-135a-3p potently modulated p38 signaling and angiogenesis in response to VEGF stimulation by targeting HIP1. These findings establish miR-135a-3p as a pivotal regulator of pathophysiological angiogenesis and tissue repair by targeting a VEGF-HIP1-p38K signaling axis, providing new targets for angiogenic therapy to promote tissue repair. | eng |
dc.description.sponsorship | U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases [P30DK034854] | |
dc.description.sponsorship | NIH National Heart, Lung, and Blood Institute [HL115141, HL117994, HL134849] | |
dc.description.sponsorship | NIH National Institute of General Medical Sciences [GM115605] | |
dc.description.sponsorship | Arthur K. Watson Charitable Trust | |
dc.description.sponsorship | Dr. Ralph and Marian Falk Medical Research Trust (Bank of America) | |
dc.description.sponsorship | American Heart Association [18SFRN33900144] | |
dc.description.sponsorship | American Diabetes Association [1-16-JDF-046] | |
dc.description.sponsorship | Watkins Discovery Award | |
dc.description.sponsorship | Lerner Young Investigator Award | |
dc.description.sponsorship | Tubitak Predoctoral Scholarship | |
dc.description.sponsorship | South-Eastern Regional Health Authorities | |
dc.description.sponsorship | Norwegian Women's Public Health Association, Norway | |
dc.language.iso | eng | |
dc.publisher | FEDERATION AMER SOC EXP BIOL | eng |
dc.relation.ispartof | Faseb Journal | |
dc.rights | restrictedAccess | eng |
dc.subject | VEGF | eng |
dc.subject | diabetic wounds | eng |
dc.subject | human organoid | eng |
dc.subject.other | huntingtin-interacting protein-1 | eng |
dc.subject.other | critical limb ischemia | eng |
dc.subject.other | growth-factor | eng |
dc.subject.other | double-blind | eng |
dc.subject.other | intermittent claudication | eng |
dc.subject.other | myocardial-infarction | eng |
dc.subject.other | impaired angiogenesis | eng |
dc.subject.other | diabetes-mellitus | eng |
dc.subject.other | gene-therapy | eng |
dc.subject.other | kinase | eng |
dc.title | MicroRNA-135a-3p regulates angiogenesis and tissue repair by targeting p38 signaling in endothelial cells | eng |
dc.type | article | eng |
dc.rights.holder | Copyright FEDERATION AMER SOC EXP BIOL | eng |
dc.identifier.doi | 10.1096/fj.201802063RR | |
dc.identifier.pmid | 30668922 | |
dc.subject.wos | Biochemistry & Molecular Biology | eng |
dc.subject.wos | Biology | eng |
dc.subject.wos | Cell Biology | eng |
dc.type.category | original article | eng |
dc.type.version | publishedVersion | eng |
hcfmusp.author.external | ICLI, Basak:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | WU, Winona:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | OZDEMIR, Denizhan:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA; Hacettepe Univ, Dept Med Biol, Ankara, Turkey | |
hcfmusp.author.external | LI, Hao:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | HAEMMIG, Stefan:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | LIU, Xin:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | GIATSIDIS, Giorgio:Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA | |
hcfmusp.author.external | CHENG, Henry S.:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | AVCI, Seyma Nazli:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | KURT, Merve:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | LEE, Nathan:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | GUIMARAES, Raphael Boesche:Fundacao Univ Cardiol ICFUC, Inst Cardiol Rio Grande Sul, Porto Alegre, RS, Brazil | |
hcfmusp.author.external | MANICA, Andre:Fundacao Univ Cardiol ICFUC, Inst Cardiol Rio Grande Sul, Porto Alegre, RS, Brazil | |
hcfmusp.author.external | RYNNING, Stein Erik:LHL Hosp Gardermoen, Dept Cardiac Surg, Jessheim, Norway | |
hcfmusp.author.external | RISNES, Ivar:LHL Hosp Gardermoen, Dept Cardiac Surg, Jessheim, Norway | |
hcfmusp.author.external | HOLLAN, Ivana:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA; Lillehamer Hosp Rheumat Dis, Rheumatol Dept, Lillehamer, Norway; Innlandet Hosp Trust, Res Dept, Brumunddal, Norway | |
hcfmusp.author.external | CROCE, Kevin:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.author.external | ORGILL, Dennis P.:Harvard Med Sch, Brigham & Womens Hosp, Dept Surg, Div Plast Surg, Boston, MA 02115 USA | |
hcfmusp.author.external | FEINBERG, Mark W.:Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Dept Med, 77 Ave Louis Pasteur,NRB-742F, Boston, MA 02115 USA | |
hcfmusp.description.beginpage | 5599 | |
hcfmusp.description.endpage | 5614 | |
hcfmusp.description.issue | 4 | |
hcfmusp.description.volume | 33 | |
hcfmusp.origem | WOS | |
hcfmusp.origem.id | WOS:000462888500077 | |
hcfmusp.origem.id | 2-s2.0-85063324571 | |
hcfmusp.publisher.city | BETHESDA | eng |
hcfmusp.publisher.country | USA | eng |
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dc.description.index | MEDLINE | eng |
dc.identifier.eissn | 1530-6860 | |
hcfmusp.citation.scopus | 53 | - |
hcfmusp.scopus.lastupdate | 2024-03-29 | - |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - HC/ICHC Artigos e Materiais de Revistas Científicas - LIM/13 Artigos e Materiais de Revistas Científicas - ODS/03 |
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