Apolipoprotein E is a pancreatic extracellular factor that maintains mature β-cell gene expression.

Autor: Ahmed I Mahmoud, Francisco X Galdos, Katherine A Dinan, Mark P Jedrychowski, Jeffrey C Davis, Ana Vujic, Inbal Rachmin, Christian Shigley, James R Pancoast, Samuel Lee, Jennifer Hollister-Lock, Catherine M MacGillivray, Steven P Gygi, Douglas A Melton, Gordon C Weir, Richard T Lee
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS ONE, Vol 13, Iss 10, p e0204595 (2018)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0204595
Popis: The in vivo microenvironment of tissues provides myriad unique signals to cells. Thus, following isolation, many cell types change in culture, often preserving some but not all of their in vivo characteristics in culture. At least some of the in vivo microenvironment may be mimicked by providing specific cues to cultured cells. Here, we show that after isolation and during maintenance in culture, adherent rat islets reduce expression of key β-cell transcription factors necessary for β-cell function and that soluble pancreatic decellularized matrix (DCM) can enhance β-cell gene expression. Following chromatographic fractionation of pancreatic DCM, we performed proteomics to identify soluble factors that can maintain β-cell stability and function. We identified Apolipoprotein E (ApoE) as an extracellular protein that significantly increased the expression of key β-cell genes. The ApoE effect on beta cells was mediated at least in part through the JAK/STAT signaling pathway. Together, these results reveal a role for ApoE as an extracellular factor that can maintain the mature β-cell gene expression profile.
Databáze: Directory of Open Access Journals
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