A sustained prostacyclin analog, ONO-1301, attenuates pancreatic fibrosis in experimental chronic pancreatitis induced by dibutyltin dichloride in rats

Yusuke Niina, Tetsuhide Ito, takamasa ono, Taichi Nakamura, Nao Fujimori, Hisato Igarashi, Yoshiki Sakai, Ryoichi Takayanagi

研究成果: ジャーナルへの寄稿記事

8 引用 (Scopus)

抄録

Background: ONO-1301, a novel sustained-release prostacyclin agonist, has an anti-fibrotic effect on the lungs, heart, and kidneys that is partly associated with the induction of hepatocyte growth factor (HGF). This study examined the anti-fibrotic effect of ONO-1301 on chronic pancreatitis (CP) progression. Methods: CP was induced in rats in vivo by dibutyltin dichloride (DBTC). Seven days after DBTC injection (day 7), a slow-release form of ONO-1301 (10 mg/kg; ONO-1301etreated group) or vehicle (DBTC-treated group) was injected. On days 14 and 28, we evaluated the histopathological CP score and mRNA expressions of HGF, cytokines, and collagen in the pancreas by real-time RT-PCR. In vitro, monocytes and pancreatic stellate cells (PSCs) were isolated from normal rat spleen and pancreas, respectively. The cytokine and collagen expressions of monocytes and PSCs were detected by real-time RT-PCR, and PSCs proliferation was examined by BrdU assay. Results: Histopathological CP scores in vivo improved in the ONO-1301etreated group compared to the DBTC-treated group, particularly inflammatory cell infiltration on day 14 and interstitial fibrosis on day 28. HGF mRNA increased significantly after ONO-1301 administration, whereas IL-1b, TNF-α, TGF-β, MCP-1, and collagen mRNA decreased significantly. Cytokine expression in monocytes was suppressed in vitro not only by HGF, but also ONO-1301 alone. However, neither ONO-1301 nor HGF affected the proliferation, or cytokine or collagen expression of PSCs. Conclusions: ONO-1301 suppresses pancreatic fibrosis in the DBTC-induced CP model by inhibiting monocyte activity not only with induction of HGF but also by ONO-1301 itself.

元の言語英語
ページ(範囲)201-210
ページ数10
ジャーナルPancreatology
14
発行部数3
DOI
出版物ステータス出版済み - 1 1 2014

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Chronic Pancreatitis
Epoprostenol
Hepatocyte Growth Factor
Pancreatic Stellate Cells
Fibrosis
Monocytes
Collagen
Cytokines
Messenger RNA
Real-Time Polymerase Chain Reaction
Pancreas
dibutyldichlorotin
ONO 1301
Bromodeoxyuridine
Spleen
Cell Proliferation
Kidney
Lung
Injections

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

これを引用

A sustained prostacyclin analog, ONO-1301, attenuates pancreatic fibrosis in experimental chronic pancreatitis induced by dibutyltin dichloride in rats. / Niina, Yusuke; Ito, Tetsuhide; ono, takamasa; Nakamura, Taichi; Fujimori, Nao; Igarashi, Hisato; Sakai, Yoshiki; Takayanagi, Ryoichi.

:: Pancreatology, 巻 14, 番号 3, 01.01.2014, p. 201-210.

研究成果: ジャーナルへの寄稿記事

Niina, Yusuke ; Ito, Tetsuhide ; ono, takamasa ; Nakamura, Taichi ; Fujimori, Nao ; Igarashi, Hisato ; Sakai, Yoshiki ; Takayanagi, Ryoichi. / A sustained prostacyclin analog, ONO-1301, attenuates pancreatic fibrosis in experimental chronic pancreatitis induced by dibutyltin dichloride in rats. :: Pancreatology. 2014 ; 巻 14, 番号 3. pp. 201-210.
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abstract = "Background: ONO-1301, a novel sustained-release prostacyclin agonist, has an anti-fibrotic effect on the lungs, heart, and kidneys that is partly associated with the induction of hepatocyte growth factor (HGF). This study examined the anti-fibrotic effect of ONO-1301 on chronic pancreatitis (CP) progression. Methods: CP was induced in rats in vivo by dibutyltin dichloride (DBTC). Seven days after DBTC injection (day 7), a slow-release form of ONO-1301 (10 mg/kg; ONO-1301etreated group) or vehicle (DBTC-treated group) was injected. On days 14 and 28, we evaluated the histopathological CP score and mRNA expressions of HGF, cytokines, and collagen in the pancreas by real-time RT-PCR. In vitro, monocytes and pancreatic stellate cells (PSCs) were isolated from normal rat spleen and pancreas, respectively. The cytokine and collagen expressions of monocytes and PSCs were detected by real-time RT-PCR, and PSCs proliferation was examined by BrdU assay. Results: Histopathological CP scores in vivo improved in the ONO-1301etreated group compared to the DBTC-treated group, particularly inflammatory cell infiltration on day 14 and interstitial fibrosis on day 28. HGF mRNA increased significantly after ONO-1301 administration, whereas IL-1b, TNF-α, TGF-β, MCP-1, and collagen mRNA decreased significantly. Cytokine expression in monocytes was suppressed in vitro not only by HGF, but also ONO-1301 alone. However, neither ONO-1301 nor HGF affected the proliferation, or cytokine or collagen expression of PSCs. Conclusions: ONO-1301 suppresses pancreatic fibrosis in the DBTC-induced CP model by inhibiting monocyte activity not only with induction of HGF but also by ONO-1301 itself.",
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T1 - A sustained prostacyclin analog, ONO-1301, attenuates pancreatic fibrosis in experimental chronic pancreatitis induced by dibutyltin dichloride in rats

AU - Niina, Yusuke

AU - Ito, Tetsuhide

AU - ono, takamasa

AU - Nakamura, Taichi

AU - Fujimori, Nao

AU - Igarashi, Hisato

AU - Sakai, Yoshiki

AU - Takayanagi, Ryoichi

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: ONO-1301, a novel sustained-release prostacyclin agonist, has an anti-fibrotic effect on the lungs, heart, and kidneys that is partly associated with the induction of hepatocyte growth factor (HGF). This study examined the anti-fibrotic effect of ONO-1301 on chronic pancreatitis (CP) progression. Methods: CP was induced in rats in vivo by dibutyltin dichloride (DBTC). Seven days after DBTC injection (day 7), a slow-release form of ONO-1301 (10 mg/kg; ONO-1301etreated group) or vehicle (DBTC-treated group) was injected. On days 14 and 28, we evaluated the histopathological CP score and mRNA expressions of HGF, cytokines, and collagen in the pancreas by real-time RT-PCR. In vitro, monocytes and pancreatic stellate cells (PSCs) were isolated from normal rat spleen and pancreas, respectively. The cytokine and collagen expressions of monocytes and PSCs were detected by real-time RT-PCR, and PSCs proliferation was examined by BrdU assay. Results: Histopathological CP scores in vivo improved in the ONO-1301etreated group compared to the DBTC-treated group, particularly inflammatory cell infiltration on day 14 and interstitial fibrosis on day 28. HGF mRNA increased significantly after ONO-1301 administration, whereas IL-1b, TNF-α, TGF-β, MCP-1, and collagen mRNA decreased significantly. Cytokine expression in monocytes was suppressed in vitro not only by HGF, but also ONO-1301 alone. However, neither ONO-1301 nor HGF affected the proliferation, or cytokine or collagen expression of PSCs. Conclusions: ONO-1301 suppresses pancreatic fibrosis in the DBTC-induced CP model by inhibiting monocyte activity not only with induction of HGF but also by ONO-1301 itself.

AB - Background: ONO-1301, a novel sustained-release prostacyclin agonist, has an anti-fibrotic effect on the lungs, heart, and kidneys that is partly associated with the induction of hepatocyte growth factor (HGF). This study examined the anti-fibrotic effect of ONO-1301 on chronic pancreatitis (CP) progression. Methods: CP was induced in rats in vivo by dibutyltin dichloride (DBTC). Seven days after DBTC injection (day 7), a slow-release form of ONO-1301 (10 mg/kg; ONO-1301etreated group) or vehicle (DBTC-treated group) was injected. On days 14 and 28, we evaluated the histopathological CP score and mRNA expressions of HGF, cytokines, and collagen in the pancreas by real-time RT-PCR. In vitro, monocytes and pancreatic stellate cells (PSCs) were isolated from normal rat spleen and pancreas, respectively. The cytokine and collagen expressions of monocytes and PSCs were detected by real-time RT-PCR, and PSCs proliferation was examined by BrdU assay. Results: Histopathological CP scores in vivo improved in the ONO-1301etreated group compared to the DBTC-treated group, particularly inflammatory cell infiltration on day 14 and interstitial fibrosis on day 28. HGF mRNA increased significantly after ONO-1301 administration, whereas IL-1b, TNF-α, TGF-β, MCP-1, and collagen mRNA decreased significantly. Cytokine expression in monocytes was suppressed in vitro not only by HGF, but also ONO-1301 alone. However, neither ONO-1301 nor HGF affected the proliferation, or cytokine or collagen expression of PSCs. Conclusions: ONO-1301 suppresses pancreatic fibrosis in the DBTC-induced CP model by inhibiting monocyte activity not only with induction of HGF but also by ONO-1301 itself.

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