title: Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy.
abstract: OBJECTIVE
  Mechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined.
  
  
  METHODS
  Pancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection.
  
  
  RESULTS
  In remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment.
  
  
  CONCLUSIONS
  aPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task.
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.|Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Ota
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.
authors.forename: Naoko Kubo
authors.initials: NK
authors.lastname: Birukawa
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.|Department of Molecular Therapeutics, Center for Food & Medical Innovation Hokkaido University, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoneda
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.|Hokkaido Laboratory of Molecular Therapeutics, Corporate Business Development Division, Nitto Denko Corporation, Hokkaido University, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nishita
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Fujita
authors.affiliation: Department of Medical Oncology and Hematology Sapporo Medical University, Sapporo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.|Hokkaido Laboratory of Molecular Therapeutics, Corporate Business Development Division, Nitto Denko Corporation, Hokkaido University, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Minomi
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.|Hokkaido Laboratory of Molecular Therapeutics, Corporate Business Development Division, Nitto Denko Corporation, Hokkaido University, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kajiwara
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.|Hokkaido Laboratory of Molecular Therapeutics, Corporate Business Development Division, Nitto Denko Corporation, Hokkaido University, Japan.
authors.forename: Miyono
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: Department of Molecular Therapeutics, Center for Food & Medical Innovation Hokkaido University, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Uchiumi
authors.affiliation: Department of Molecular Therapeutics, Center for Food & Medical Innovation Hokkaido University, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Mikuni
authors.affiliation: Department of Molecular Therapeutics, Center for Food & Medical Innovation Hokkaido University, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Mizuguchi
authors.affiliation: Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Meguro
authors.affiliation: Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Surgery, Surgical Oncology & Science, Sapporo Medical University, Sapporo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Molecular Target Exploration, Sapporo Medical University, Sapporo, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Niitsu
mesh_terms: D061354:Acinar Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D015870:Gene Expression; D050958:HSP47 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D010180:Pancreatectomy / Q000534:rehabilitation*; D058954:Pancreatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014801:Vitamin A / Q000737:chemistry / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D050958:HSP47 Heat-Shock Proteins; D008081:Liposomes; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; C494662:Serpinh1 protein, rat; D014801:Vitamin A