title: Estrogen Receptor α Regulates β-Cell Formation During Pancreas Development and Following Injury.
abstract: Identifying pathways for β-cell generation is essential for cell therapy in diabetes. We investigated the potential of 17β-estradiol (E2) and estrogen receptor (ER) signaling for stimulating β-cell generation during embryonic development and in the severely injured adult pancreas. E2 concentration, ER activity, and number of ERα transcripts were enhanced in the pancreas injured by partial duct ligation (PDL) along with nuclear localization of ERα in β-cells. PDL-induced proliferation of β-cells depended on aromatase activity. The activation of Neurogenin3 (Ngn3) gene expression and β-cell growth in PDL pancreas were impaired when ERα was turned off chemically or genetically (ERα(-/-)), whereas in situ delivery of E2 promoted β-cell formation. In the embryonic pancreas, β-cell replication, number of Ngn3(+) progenitor cells, and expression of key transcription factors of the endocrine lineage were decreased by ERα inactivation. The current study reveals that E2 and ERα signaling can drive β-cell replication and formation in mouse pancreas.
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Yixing
authors.initials: Y
authors.lastname: Yuchi
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Legein
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Groef
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Gunter
authors.initials: G
authors.lastname: Leuckx
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Violette
authors.initials: V
authors.lastname: Coppens
authors.affiliation: Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Van Overmeire
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium Department of Pediatrics, Division of Pediatric Endocrinology, Ghent University Hospital, and Department of Pediatrics and Medical Genetics, Ghent University, Ghent, Belgium.
authors.forename: Willem
authors.initials: W
authors.lastname: Staels
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Nico
authors.initials: N
authors.lastname: De Leu
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Martens
authors.affiliation: Myeloid Cell Immunology Laboratory, Vlaams Instituut voor Biotechnologie, Brussels, Belgium Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium harry.heimberg@vub.ac.be.
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
authors.affiliation: Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: Van de Casteele
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000196:embryology*; D010183:Pancreatic Ducts / Q000293:injuries*; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004958:Estradiol; D047628:Estrogen Receptor alpha; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C407737:Neurog3 protein, mouse