Involvement of Pancreatic Stellate Cells in Regeneration of Remnant Pancreas after Partial Pancreatectomy

• Published in: PloS one Vol. 11; no. 12; p. e0165747
• Main Authors: Ota, Shigenori, Nishimura, Miyuki, Murakami, Yuya, Birukawa, Naoko Kubo, Yoneda, Akihiro, Nishita, Hiroki, Fujita, Ryosuke, Sato, Yasushi, Minomi, Kenjiro, Kajiwara, Keiko, Miyazaki, Miyono, Uchiumi, Maki, Mikuni, Shintaro, Tamura, Yasuaki, Mizuguchi, Toru, Imamura, Masafumi, Meguro, Makoto, Kimura, Yasutoshi, Hirata, Koichi, Niitsu, Yoshiro
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.12.2016; Public Library of Science (PLoS)
• Subjects: Acinar cells; Acinar Cells - cytology; Acinar Cells - metabolism; Animals; Apoptosis; Augmentation; Biology and Life Sciences; Biomarkers - metabolism; Cell culture; Cell growth; Cell Proliferation; Cells (biology); Coculture Techniques; Collagen; Diabetes; Experiments; Extracellular matrix; Gastroenterology; Gene Expression; HSP47 Heat-Shock Proteins - antagonists & inhibitors; HSP47 Heat-Shock Proteins - genetics; HSP47 Heat-Shock Proteins - metabolism; Islet cells; Islets of Langerhans - cytology; Islets of Langerhans - metabolism; Laboratory animals; Lip; Liposomes - administration & dosage; Liposomes - chemistry; Male; Medical research; Medicine and Health Sciences; Pancreas; Pancreas - drug effects; Pancreas - metabolism; Pancreas - pathology; Pancreas - surgery; Pancreatectomy; Pancreatectomy - rehabilitation; Pancreatic Stellate Cells - cytology; Pancreatic Stellate Cells - metabolism; Pancreatitis; Polymerase chain reaction; Progenitor cells; Rats; Rats, Sprague-Dawley; Regeneration; Regeneration - physiology; Research and Analysis Methods; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Rodents; siRNA; Sox9 protein; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism; Stellate cells; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Vitamin A; Vitamin A - chemistry; Vitamin A - pharmacology; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0165747

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. 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. 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. 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.