title: Periostin induces pancreatic regeneration.
abstract: We found that the secreted protein periostin (Postn) is highly induced after partial pancreatectomy in regenerating areas containing mesenchymal stroma and tubular complexes. Importantly, after partial pancreatectomy, Postn-deficient mice exhibit impaired mesenchymal formation and reduced regeneration specifically within the pancreatic β-cell compartment. Furthermore, Postn-deficient mice demonstrate an increased sensitivity to streptozotocin. Notably, injection of Postn directly into the pancreas stimulated proliferation of vimentin-expressing cells within 24 hours, and by 3 days, a mesenchymal stroma was present containing proliferating duct-like cells expressing the progenitor markers Ngn3 and Pdx1. Intraperitoneal injection of Postn resulted in increased numbers of islets and long-term glucoregulatory benefits with no adverse effects found in other tissues. Delivery of Postn throughout the pancreas via the common bile duct resulted in increased numbers of small insulin-expressing clusters and a significant improvement in glucose tolerance. Therefore, Postn is novel molecule capable of potentiating pancreatic β-cell regeneration.
authors.affiliation: Sprott Center for Stem Cell Research (J.K.S., S.F., M.A.R.), Ottawa Hospital Research Institute, Regenerative Medicine Program, and University of Ottawa (J.K.S., M.A.R.), Cellular and Molecular Medicine, Faculty of Medicine, Ottawa, Ontario, Canada K1H 8L6.
authors.forename: Johnathan K
authors.initials: JK
authors.lastname: Smid
authors.forename: Sharlene
authors.initials: S
authors.lastname: Faulkes
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000502:physiology*; D010180:Pancreatectomy; D012038:Regeneration / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D015815:Cell Adhesion Molecules; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C407737:Neurog3 protein, mouse; C082838:Postn protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein