Elucidation of zinc transporter's role for salivary development and regeneration

• Project/Area Number: 25462874
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Showa University
• Principal Investigator: Yamamoto Go 昭和大学, 歯学部, 兼任講師 (80384189)
• Co-Investigator(Kenkyū-buntansha): MISHIMA Kenji 昭和大学, 歯学部, 教授 (50275343) ; KOHNO Yohko 昭和大学, 歯学部, 准教授 (40195681) ; IRIE Tarou 昭和大学, 歯学部, 講師 (00317570) ; YASUHARA Rika 昭和大学, 歯学部, 助教 (20453649) ; TANAKA Junichi 昭和大学, 歯学部, 助教 (40710166) ; FUKADA Toshiyuki 徳島文理大学, 薬学部, 教授 (70373363) ; SUGIYA Hiroshi 日本大学, 生物資源科学部, 教授 (20050114) ; FUKUSHIMA Miwako 昭和大学, 歯学部, 助教 (90548273)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 唾液腺 / 亜鉛輸送体 / ZIP10 / 亜鉛 / 放射線照射 / 再生 / 発生 / トランスポーター / ZIP6

Outline of Final Research Achievements

Homeostasis of intracellular zinc level is regulated by zinc transporter (ZIP). We hypothesized that zinc transporter family is inovolved in salivary gland development and regeneration. In the analysis of ZIP6 knockout mouse, there is no morphological difference of salivary glands between knockout mouse and wild one. It is suggested that ZIP6 may participate in water secretion but not in protein secretion. ZIP10 was found to be inhibition of cell death of NS-SV-DC (human normal salivary gland cell lines showing ductal cell phenotype) induced by irradiation. These results may be expected to give important finding for ZIP10 to be a promising target molecule of dry mouth and be of some benefit for renewed medical treatment of saliva secretion disorder by using control of ZIP10 expression.

Research Products

• [Journal Article] Comparing Gene Expression during Cadmium Uptake and Distribution: Untreated vs Oral Cd-Treated Wild-Type and ZIP14 Knockout Mice. (2014)
  • Author(s): Jorge-Nebert, LF., M. Galvez-Peralta, JL. Figueroa, M. Somarathna, S. Hojyo, T. Fukada, and DW. Nebert.
  • Journal Title: Toxicological Sciences Volume: 204 Issue: 1 Pages: 26-35
  • DOI: 10.1093/toxsci/kfu204
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B cell receptor signal strength. (2014)
  • Author(s): Hojyo, S., T. Miyai, H. Fujishiro, M. Kawamura, T. Yasuda, A. Hijikata, BH. Bin, T. Irie, J. Tanaka, T. Atsumi, M. Murakami, M. Nakayama, O. Ohara, S. Himeno, H. Yoshida, H. Koseki, T. Ikawa, K. Mishima, and T. Fukada.
  • Journal Title: PNAS Volume: 111 Pages: 11786-11791
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Molecular pathogenesis of spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins. (2014)
  • Author(s): Bin et al.
  • Journal Title: EMBO Molecular Medicine Volume: 6 Issue: 8 Pages: 1028-1042
  • DOI: 10.15252/emmm.201303809
  • Peer Reviewed
• [Journal Article] Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development (2014)
  • Author(s): Miyai T, Hojyo S, Ikawa T, Kawamura M, Irie T, Ogura H, Hijikata A, Bin BH, Yasuda T, Kitamura H, Nakayama M, Ohara O, Yoshida H, Koseki H, Mishima K, Fukada T
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 111 Issue: 32 Pages: 11780-11785
  • DOI: 10.1073/pnas.1323549111
  • Peer Reviewed / Open Access
• [Journal Article] B-cell receptor signal strength and zinc signaling: unraveling the role of zinc transporter ZIP10 in humoral immunity. (2014)
  • Author(s): Hojyo, S., T. Miyai, and Fukada T.
  • Journal Title: Receptors & Clinical Investigation Volume: 2 Pages: 1-4
  • DOI: 10.14800/rci.387
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Downregulation of carbonic anhydrase IX promotes Col10a1 expression in chondrocytes (2013)
  • Author(s): Maruyama T, Miyamoto Y, Yamamoto G, Yamada A, Yoshimura K, Suzawa T, Takami M, Akiyama T, Hoshino M, Iwasa F, Ikumi N, Tachikawa T, Mishima K, Baba K, Kamijo R
  • Journal Title: PLoS ONE Volume: Vol.8 Issue: 2 Pages: e56984-e56984
  • DOI: 10.1371/journal.pone.0056984
  • Peer Reviewed
• [Journal Article] Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma. (2013)
  • Author(s): Hayashi S, Tanaka J, Okada S, Isobe T, Yamamoto G, Yasuhara R, Irie T, Akiyama C, Kohno Y, Tachikawa T, Mishima K.
  • Journal Title: Exp Cell Res Volume: 319 Issue: 8 Pages: 1220-1228
  • DOI: 10.1016/j.yexcr.2013.03.004
  • Peer Reviewed
• [Presentation] ZIP10-mediated zinc signaling is required for B-cell maintainance (2015)
  • Author(s): Tomohiro Miyai，Shintaro Hojyo，Tomokatsu Ikawa，Bum-Ho Bin，Tarou Irie，Junichi Tanaka， Toshiyuki Fukada and Kenji Mishima
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-04-30
  • Int'l Joint Research
• [Presentation] 亜鉛シグナル：B細胞の恒常性を司る新しい制御機構 (2014)
  • Author(s): 深田俊幸、宮井智浩、北條慎太郎、美島健二
  • Organizer: 心血管膜輸送研究会 2014
  • Place of Presentation: 岡崎
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] 亜鉛シグナル：生体恒常性を統御する新しい情報伝達機構 (2014)
  • Author(s): 深田俊幸
  • Organizer: 第87回日本内分泌学会学術総会教育講演
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24 – 2014-04-26
  • Invited
• [Presentation] 亜鉛による情報伝達：健康と病気への関与 (2014)
  • Author(s): 深田俊幸
  • Organizer: 第56回歯科基礎医学会学術大会・総会シンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2014-04-24 – 2014-04-26
• [Book] Signals in Cellular Functions and Disorders (2014)
  • Author(s): Fukada, T, Hojyo, S., and Bin, B.H.
  • Total Pages: 345
  • Publisher: Springer
• [Remarks] 唾液腺再生医療プロジェクト
  • URL: http://www10.showa-u.ac.jp/~oralpath/project.html
• [Remarks] 唾液腺再生医療プロジェクト
  • URL: http://www10.showa-u.ac.jp/~oralpath/project.html