ID 112310
Title Alternative
Role of PSCs in Regeneration of Remnant Pancreas after PX
Author
Ota, Shigenori Sapporo Medical University
Nishimura, Miyuki Sapporo Medical University
Murakami, Yuya Sapporo Medical University
Kubo Birukawa, Naoko Sapporo Medical University
Yoneda, Akihiro Sapporo Medical University|Hokkaido University
Nishita, Hiroki Sapporo Medical University|Nitto Denko Corporation
Fujita, Ryosuke Sapporo Medical University
Minomi, Kenjiro Sapporo Medical University|Nitto Denko Corporation
Kajiwara, Keiko Sapporo Medical University|Nitto Denko Corporation
Miyazaki, Miyono Sapporo Medical University|Nitto Denko Corporation
Uchiumi, Maki Hokkaido University
Mikuni, Shintaro Hokkaido University
Tamura, Yasuaki Hokkaido University
Mizuguchi, Toru Sapporo Medical University
Imamura, Masafumi Sapporo Medical University
Meguro, Makoto Sapporo Medical University
Kimura, Yasutoshi Sapporo Medical University
Hirata, Koichi Sapporo Medical University
Niitsu, Yoshiro Sapporo Medical University
Content Type
Journal Article
Description
Background and objectives
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.

Conclusion
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.
Journal Title
PLOS ONE
ISSN
19326203
Publisher
PLOS
Volume
11
Issue
12
Start Page
e0165747
Published Date
2016-12-09
Rights
Copyright: © 2016 Ota et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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DOI (Published Version)
URL ( Publisher's Version )
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language
eng
TextVersion
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departments
Medical Sciences