Elucidation of the micro-RNA-mediated regulation of pancreatic stellate cell activation and its therapeutic applications.

• Project/Area Number: 20590803
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: MASAMUNE Atsushi Tohoku University, 病院, 助教 (90312579)
• Co-Investigator(Kenkyū-buntansha): SATOH Kennichi 東北大学, 病院, 講師 (10282055)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 膵炎 / 膵癌 / 線維化 / マイクロRNA / 上皮間葉転換 / 放射線治療 / 膵星細胞 / interleukin-33 / 慢性膵炎 / 膵線維化

Research Abstract

There is accumulating evidence that pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with chronic pancreatitis and pancreatic cancer. We compared microRNA expression profiles between freshly-isolated (quiescent) rat PSCs and culture-activated PSCs. We found that the expression of miR-100, miR-128, miR-143 was increased whereas that of miR-126 and miR-200 was decreased upon activation by culture in serum-containing medium. The functional consequences of these alternations are currently under investigation.

Research Products

• [Journal Article] Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling. (2011)
  • Author(s): Mantoni TS, Lunardi S, Al-Assar O, Masamune A, Brunner TB.
  • Journal Title: Cancer Res. in press
  • Peer Reviewed
• [Journal Article] The evaluation of MSX2 mRNA expression level in biliary brush cytological specimens. (2011)
  • Author(s): Ito H, Satoh K, Hamada S, Hirota M, Kanno A, Ishida K, Unno J, Masamune A, Katayose Y, Unno M, Shimosegawa T.
  • Journal Title: Anticancer Res. 31 Pages: 1011-1017
  • Peer Reviewed
• [Journal Article] The homeobox gene MSX2 determines chemosensitivity of pancreatic cancer cells via the regulation of transporter gene ABCG2. (2011)
  • Author(s): Hamada S, Satoh K, Hirota M, Kanno A, Umino J, Ito H, Masamune A, Kikuta K, Kume K, Shimosegawa T.
  • Journal Title: J Cell Physiol. in press
  • Peer Reviewed
• [Journal Article] Genetic background is different between sentinel and recurrent acute pancreatitis. (2011)
  • Author(s): Masamune A, Ariga H, Kume K, Kakuta Y, Satoh K, Satoh A, Shimosegawa T.
  • Journal Title: J Gastroenterol Hepatol. in press
  • Peer Reviewed
• [Journal Article] Calcium-binding protein S100P is a novel diagnostic marker of cholangiocarcinoma. (2011)
  • Author(s): Hamada S, Satoh K, Hirota M, Kanno A, Ishida K, Umino J, Ito H, Kikuta K, Kume K, Masamune A, Katayose Y, Unno M, Shimosegawa T.
  • Journal Title: Cancer Sci. 102 Pages: 150-156
  • NAID: 10029288859
  • Peer Reviewed
• [Journal Article] Evaluation of MSX2 mRNA in brush cytology specimens distinguished pancreatic carcinoma from chronic pancreatitis. (2011)
  • Author(s): Satoh K, Hamada S, Kanno A, Ishida K, Ito H, Hirota M, Masamune A, Egawa S, Unno M, Shimosegawa T.
  • Journal Title: Cancer Sci. 102 Pages: 157-161
  • NAID: 10029288885
  • Peer Reviewed
• [Journal Article] Pancreatic stellate cells radioprotect pancreatic cancer cells through β1-integrin signaling (2011)
  • Author(s): Mantoni T, et al.
  • Journal Title: Cancer Res
  • Peer Reviewed
• [Journal Article] Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells. (2010)
  • Author(s): Kikuta K, Masamune A, Watanabe T, Ariga H, Itoh H, Hamada S, Satoh K, Egawa S, Unno M, Shimosegawa T.
  • Journal Title: Biochem Biophys Res Commun. 403 Pages: 380-384
  • Peer Reviewed
• [Journal Article] Nuclear expression of interleukin-33 in pancreatic stellate cells. (2010)
  • Author(s): Masamune A, Watanabe T, Kikuta K, Satoh K, Kanno A, Shimosegawa T.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. 299
  • Peer Reviewed
• [Journal Article] -651C/T promoter polymorphism in the CD14 gene is associated with severity of acute pancreatitis in Japan. (2010)
  • Author(s): Masamune A, Kume K, Kikuta K, Watanabe T, Hirota M, Satoh K, Kanno A, Suzuki N, Kakuta Y, Shimosegawa T.
  • Journal Title: J Gastroenterol. 45 Pages: 225-233
  • NAID: 10027214689
  • Peer Reviewed
• [Journal Article] Effects of ethanol and its metabolites on human pancreatic stellate cells. (2010)
  • Author(s): Masamune A, Satoh A, Watanabe T, Kikuta K, Satoh M, Suzuki N, Satoh K, Shimosegawa T.
  • Journal Title: Dig Dis Sci. 55 Pages: 204-211
  • Peer Reviewed
• [Journal Article] Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells. (2010)
  • Author(s): Kikuta K, et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 403 Pages: 380-384
  • Peer Reviewed
• [Journal Article] Nuclear expression of interleukin-33 in pancreatic stellate cells. (2010)
  • Author(s): Masamune A, et al.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 299
  • Peer Reviewed
• [Journal Article] Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis. (2009)
  • Author(s): Masamune A, Watanabe T, Kikuta K, Shimosegawa T.
  • Journal Title: Clin Gastroenterol Hepatol. 7
  • Peer Reviewed
• [Journal Article] Bone marrow contributes to the population of pancreatic stellate cells in mice. (2009)
  • Author(s): Watanabe T, Masamune A, Kikuta K, Hirota M, Kume K, Satoh K, Shimosegawa T.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. 297
  • Peer Reviewed
• [Journal Article] LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells. (2009)
  • Author(s): Unno J, Satoh K, Hirota M, Kanno A, Hamada S, Ito H, Masamune A, Tsukamoto N, Motoi F, Egawa S, Unno M, Horii A, Shimosegawa T.
  • Journal Title: Int J Oncol. 35 Pages: 813-821
  • Peer Reviewed
• [Journal Article] Signal transduction in pancreatic stellate cells. (2009)
  • Author(s): Masamune A, Shimosegawa T.
  • Journal Title: J Gastroenterol. 44 Pages: 249-260
  • NAID: 10025173977
  • Peer Reviewed
• [Journal Article] Fibrinogen induces cytokine and collagen production in pancreatic stellate cells. (2009)
  • Author(s): Masamune A, Kikuta K, Watanabe T, Satoh K, Hirota M, Hamada S, Shimosegawa T.
  • Journal Title: Gut 58 Pages: 550-559
  • Peer Reviewed
• [Journal Article] A loss-of-function p.G191R variant in the anionic trypsinogen (PRSS2) gene in Japanese patients with pancreatic disorders. (2009)
  • Author(s): Kume K, Masamune A, Takagi Y, Kikuta K, Watanabe T, Satoh K, Satoh A, Hirota M, Hamada S, Shimosegawa T.
  • Journal Title: Gut 58 Pages: 820-824
  • Peer Reviewed
• [Journal Article] Ellagic acid inhibits pancreatic fibrosis in male Wistar Bonn/Kobori rats. (2009)
  • Author(s): Suzuki N, Masamune A, Kikuta K, Watanabe T, Satoh K, Shimosegawa T.
  • Journal Title: Dig Dis Sci. 54 Pages: 802-810
  • Peer Reviewed
• [Journal Article] Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis (2009)
  • Author(s): Masamune A, et al.
  • Journal Title: Clin Gastroenterol Hepatol 11
  • Peer Reviewed
• [Journal Article] Bone marrow contributes to the population of pancreatic stellate cells in mice. (2009)
  • Author(s): Watanabe T, Masamune A, et al.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 297
  • Peer Reviewed
• [Journal Article] Signal transduction in pancreatic stellate cells. (2009)
  • Author(s): Masamune A, et al.
  • Journal Title: J Gastroenterol 44 Pages: 249-260
  • NAID: 10025173977
  • Peer Reviewed
• [Journal Article] Fibrinogen induces cytokine and collagen production in pancrea tic stellate cells (2009)
  • Author(s): Masamune A, et.al.
  • Journal Title: Gut 58 Pages: 550-559
  • Peer Reviewed
• [Journal Article] Signal transduction in pancreatic stellate cells (2009)
  • Author(s): Masamune A, et.al.
  • Journal Title: J Gastroentetol 44 Pages: 249-260
  • NAID: 10025173977
  • Peer Reviewed
• [Journal Article] Stromal SPARC expression and patient survival after chemoradiation for non-resectable pancreatic adenocarcinoma. (2008)
  • Author(s): Mantoni TS, Schendel RR, Rodel F, Niedobitek G, Al-Assar O, Masamune A, Brunner TB.
  • Journal Title: Cancer Biol Ther. 7 Pages: 1806-1815
  • Peer Reviewed
• [Journal Article] Hypoxia stimulates pancreatic stellate cells to induce fibrosis and angiogenesis in pancreatic cancer. (2008)
  • Author(s): Masamune A, Kikuta K, Watanabe T, Satoh K, Hirota M, Shimosegawa T.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol. 295
  • Peer Reviewed
• [Journal Article] Hypoxia stimulates pancreatic stellate cells to induce fibrosis and angiogenesis in pancreatic cancer (2008)
  • Author(s): Masamune A, et.al.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 295
  • Peer Reviewed
• [Presentation] Hedgehog signaling pathway mediates activation of pancreatic stellate cells. (2010)
  • Author(s): 正宗淳, 菊田和宏, 渡辺崇, 下瀬川徹
  • Organizer: United European Gastroenterology Week.
  • Place of Presentation: Barcelona, Spain.
  • Year and Date: 2010-10-26
• [Presentation] Hedgehog signaling pathway mediates activation of pancreatic stellate cells (2010)
  • Author(s): Masamune A, et al.
  • Organizer: United European Gastroenterology Week
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2010-10-26
• [Presentation] Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis. (2009)
  • Author(s): Masamune A, et al.
  • Organizer: Joint meeting of American Pancreatic Association & Japan Pancreas Society
  • Place of Presentation: Honolulu, Hawaii, USA
  • Year and Date: 2009-11-05
• [Presentation] Advanced glycation end-productsは膵星細胞の増殖を促進する (2009)
  • Author(s): 菊田和宏、正宗淳、渡辺崇、下瀬川徹
  • Organizer: 第40回日本消化器病学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-31
• [Presentation] Roles of pancreatic stellate cells in pancreatic fibrosis and inflammation. (2009)
  • Author(s): 正宗淳, 下瀬川徹
  • Organizer: AGA-JSGE Joint Meeting.
  • Place of Presentation: Sapporo.
  • Year and Date: 2009-05-07
• [Presentation] Advanced glycation end-productsは膵星細胞の増殖とMCP-1産生を誘導する (2009)
  • Author(s): 菊田和宏、正宗淳、下瀬川徹
  • Organizer: 第95回日本消化器病学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-05-07
• [Presentation] 膵線維化の分子機序-最新の知見- (2009)
  • Author(s): 正宗淳
  • Organizer: 第4回新都心消化器カンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2009-04-07
• [Presentation] フィブリノゲンはヒト膵星細胞のサイトカイン産生とコラーゲン産生を刺激する (2008)
  • Author(s): 正宗淳, ほか
  • Organizer: J-DDW
  • Place of Presentation: 東京
  • Year and Date: 2008-10-02
• [Presentation] 膵星細胞からみた膵線維化の分子機序 (2008)
  • Author(s): 正宗淳
  • Organizer: DDW-Japan 2008
  • Place of Presentation: 東京
  • Year and Date: 2008-10-01
• [Presentation] フィブリノゲンはヒト膵星細胞におけるサイトカインとコラーゲン産生を誘導する (2008)
  • Author(s): 正宗淳、菊田和宏、渡辺崇、佐藤賢一、下瀬川徹
  • Organizer: DDW-Japan 2008
  • Place of Presentation: 東京
  • Year and Date: 2008-10-01