Circulating Igf-i And Igfbp3 Levels Control Human Colonic Stem Cell Function And Are Disrupted In Diabetic Enteropathy

dc.creatorD'Addio
dc.creatorFrancesca; La Rosa
dc.creatorStefano; Maestroni
dc.creatorAnna; Jung
dc.creatorPeter; Orsenigo
dc.creatorElena; Ben Nasr
dc.creatorMoufida; Tezza
dc.creatorSara; Bassi
dc.creatorRoberto; Finzi
dc.creatorGiovanna; Marando
dc.creatorAlessandro; Vergani
dc.creatorAndrea; Frego
dc.creatorRoberto; Albarello
dc.creatorLuca; Andolfo
dc.creatorAnnapaola; Manuguerra
dc.creatorRoberta; Viale
dc.creatorEdi; Staudacher
dc.creatorCarlo; Corradi
dc.creatorDomenico; Batlle
dc.creatorEduard; Breault
dc.creatorDavid; Secchi
dc.creatorAntonio; Folli
dc.creatorFranco; Fiorina
dc.creatorPaolo
dc.date2015-OCT
dc.date2016-06-07T13:20:02Z
dc.date2016-06-07T13:20:02Z
dc.date.accessioned2018-03-29T01:40:09Z
dc.date.available2018-03-29T01:40:09Z
dc.identifier
dc.identifierCirculating Igf-i And Igfbp3 Levels Control Human Colonic Stem Cell Function And Are Disrupted In Diabetic Enteropathy. Cell Press, v. 17, p. 486-498 OCT-2015.
dc.identifier1934-5909
dc.identifierWOS:000365693800014
dc.identifier10.1016/j.stem.2015.07.010
dc.identifierhttp://www.sciencedirect.com/science/article/pii/S1934590915003094
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/242820
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1306518
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionThe role of circulating factors in regulating colonic stem cells (CoSCs) and colonic epithelial homeostasis is unclear. Individuals with long-standing type 1 diabetes (T1D) frequently have intestinal symptoms, termed diabetic enteropathy (DE), though its etiology is unknown. Here, we report that T1D patients with DE exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed altered levels of insulin-like growth factor 1 (IGF-I) and its binding protein 3 (IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via binding its receptor TMEM219, in an IGF-I-independent manner, and disrupted in vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in patients with long-standing T1D via kidney-pancreas transplantation or in diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized circulating IGF-I/IGFBP3 levels and reestablished CoSC homeostasis. These findings demonstrate that peripheral IGF-I/IGFBP3 controls CoSCs and their dysfunction in DE.
dc.description17
dc.description4
dc.description
dc.description486
dc.description498
dc.descriptionItalian Scientists and Scholars of North America Foundation (ISSNAF)-Fondazione Marche Fellowship
dc.descriptionADA mentor-based fellowship
dc.descriptionEFSD/Sanofi European Research Programme
dc.descriptionAmerican Heart Association (AHA)
dc.descriptionAST fellowship
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description[RF-2010-2314794]
dc.description[RF-2010-233119]
dc.description[RO1DK084056]
dc.description[P30DK034854]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description
dc.description
dc.description
dc.languageen
dc.publisherCELL PRESS
dc.publisher
dc.publisherCAMBRIDGE
dc.relationCELL STEM CELL
dc.rightsfechado
dc.sourceWOS
dc.subjectKidney-pancreas Transplantation
dc.subjectStage Renal-disease
dc.subjectGastrointestinal Symptoms
dc.subjectColorectal-cancer
dc.subjectDialysis Patients
dc.subjectNatural-history
dc.subjectGrowth-factors
dc.subjectInsulin
dc.subjectMellitus
dc.subjectComplications
dc.titleCirculating Igf-i And Igfbp3 Levels Control Human Colonic Stem Cell Function And Are Disrupted In Diabetic Enteropathy
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución