Maintenance mechanism of anterior pituitary progenitor cells by homophilic cell adhesion

• Project/Area Number: 25460275
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Jichi Medical University
• Principal Investigator: Kikuchi Motoshi 自治医科大学, 医学部, 教授 (60332988)
• Co-Investigator(Kenkyū-buntansha): AZUMA Morio 自治医科大学, 医学部, 助教 (90709643) ; YASHIRO Takashi 自治医科大学, 医学部, 教授 (80119859)
• 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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 下垂体前葉 / 細胞分化 / カドヘリン / Notch / 下垂体 / cadherin / 前駆細胞 / 腺下垂体 / 細胞接着 / 細胞間相互作用 / 細胞接着因子 / Notchシグナル

Outline of Final Research Achievements

The anterior pituitary is composed of types of hormone-producing cells. Progenitor cells that can differentiate into the types of cells were reported to be maintained in adult tissue. Differentiation is regulated by humoral factors, however, the mechanism to maintain progenitor cells was not understood. We previously showed Notch signaling, a regulator of progenitor cells in many organs, is activated in particular cell aggregates in rat pituitary. In this study, immunohistochemistry revealed a close relationship between Notch signaling molecules and cell adhesion molecule E-cadherin. Expression of the target HES1 decreased by E-cadherin inhibition in primary culture. Notch receptor and ligand were always co-localized within cells, suggesting homologous cells have reciprocal effects. We are further analyzing genes regulated by Notch signaling. The present study suggests that E-cadherin-mediated cell attachment is responsible for maintenance of progenitor cells through Notch signaling.

Research Products

• [Journal Article] Folliculostellate cell interacts with pericyte via TGFbeta2 in rat anterior pituitary. (2016)
  • Author(s): Tsukada T, Azuma M, Horiguchi K, Fujiwara K, Kouki T, Kikuchi M, Yashiro T.
  • Journal Title: J Endocrinol Volume: JOE-16-0033
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells. (2016)
  • Author(s): Maliza R, Fujiwara K, Tsukada T, Azuma M, Kikuchi M, Yashiro T.
  • Journal Title: Endocr J Volume: Epub
  • NAID: 130005159557
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Maintenance of the Extracellular Matrix in Rat Anterior Pituitary Gland: Identification of Cells Expressing Tissue Inhibitors of Metalloproteinases (2015)
  • Author(s): Azuma M, Tofrizal A, Maliza R, Batchuluun K, Ramadhani D, Syaidah R, Tsukada T, Fujiwara K, Kikuchi M, Horiguchi K, Yashiro T
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 48 Issue: 6 Pages: 185-192
  • DOI: 10.1267/ahc.15020
  • NAID: 130005116785
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed
• [Journal Article] Expression of the heparin-binding growth factor midkine and its receptor, Ptprz1, in adult rat pituitary (2014)
  • Author(s): Fujiwara K, Horiguchi K, Maliza R, Tofrizal A, Batchuluun K, Ramadhani D, Syaidah R, Tsukada T, Azuma M, Kikuchi M, Yashiro T
  • Journal Title: Cell Tissue Res Volume: 359 Issue: 3 Pages: 909-914
  • DOI: 10.1007/s00441-014-2073-8
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Changes in Laminin Chain Expression in Pre- and Postnatal Rat Pituitary Gland (2014)
  • Author(s): Ramadhani D, Tsukada T, Fujiwara K, Azuma M, Kikuchi M, Yashiro T
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 47 Issue: 5 Pages: 231-237
  • DOI: 10.1267/ahc.14031
  • NAID: 130004700244
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Folliculostellate Cells Are Required for Laminin Release from Gonadotrophs in Rat Anterior Pituitary (2014)
  • Author(s): Tsukada T, Fujiwara K, Horiguchi K, Azuma M, Ramadhani D, Tofrizal A, Batchuluun K, Maliza R, Syaidah R, Kikuchi M, Yashiro T
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 47 Issue: 5 Pages: 239-245
  • DOI: 10.1267/ahc.14036
  • NAID: 130004700245
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In situ hybridization analysis of the temporospatial expression of the midkine/pleiotrophin family in rat embryonic pituitary gland (2014)
  • Author(s): Fujiwara K,他9名
  • Journal Title: Cell Tissue Res. Volume: 357 Issue: 1 Pages: 337-344
  • DOI: 10.1007/s00441-014-1875-z
  • Peer Reviewed
• [Journal Article] Reassembly of Anterior Pituitary Organization by Hanging Drop Three-Dimensional Cell Culture (2013)
  • Author(s): Tsukada T, Kouki T, Fujiwara K, Ramadhani D, Horiguchi K, Kikuchi M, and Yashiro T
  • Journal Title: ACTA HISTOCHEMICA ET CYTOCHEMICA Volume: 46 Issue: 4 Pages: 121-127
  • DOI: 10.1267/ahc.13015
  • NAID: 130003361079
  • ISSN: 0044-5991, 1347-5800
  • Peer Reviewed
• [Presentation] Identification of T-cadherin as a novel proliferation associated protein on folliculo-stellatecellsin ratanterior pituitary (2016)
  • Author(s): Khongorzul Batchuluun et al.
  • Organizer: 第121回 日本解剖学会総会・全国学術集会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 2016-03-30
• [Presentation] Gene expression analysis of folliculostellate cells in ‘transitional zone’ of anterior pituitary gland of rat – special relevance to circadian rhythm – (2015)
  • Author(s): Rita Maliza et al.
  • Organizer: 第30回日本下垂体研究会
  • Place of Presentation: 富山県黒部市
  • Year and Date: 2015-08-05
• [Presentation] E-cadherin mediates Notch signaling in the rat anterior pituitary (2015)
  • Author(s): Batchuluun K, Azuma M, Yashiro T, Kikuchi M
  • Organizer: 第120回 日本解剖学会総会･全国学術集会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Identification of tissue inhibitors of metalloproteinases-expressing cells in rat anterior pituitary gland (2014)
  • Author(s): Azuma M, Batchuluun K, Fujiwara K, Tsukada T, Kikuchi M, Yashiro T
  • Organizer: The 8th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology
  • Place of Presentation: 愛知県岡崎市
  • Year and Date: 2014-11-07 – 2014-11-09
• [Presentation] 細胞接着因子カドヘリンから腺下垂体前駆細胞を考える (2014)
  • Author(s): 菊地元史
  • Organizer: 第 18 回日本内分泌病理学会学術総会
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2014-11-01 – 2014-11-02
  • Invited
• [Presentation] . Histological and functional characterization of Notch signaling in the adult rat pituitary gland (2014)
  • Author(s): Batchuluun K, Azuma M, Yashiro T, Kikuchi M
  • Organizer: 第４１回日本神経内分泌学会学術集会プログラム
  • Place of Presentation: 東京都千代田区
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Effect of Notch2 signaling on cell proliferation and Sox2 expression in S100b-positive cells in the rat pituitary gland (2014)
  • Author(s): Batchuluun K, Azuma M, Yashiro T, Kikuchi M
  • Organizer: 第29回日本下垂体研究会学術集会
  • Place of Presentation: 東京都八王子市
  • Year and Date: 2014-08-08 – 2014-08-10
• [Presentation] ラット下垂体前葉におけるエンケファリン前駆体遺伝子発現細胞の同定 (2014)
  • Author(s): 藤原 研、塚田 岳大、東 森生、Dini Ramadhani、Tofrizal bin Alimuddin、Rita Maliza、Khongorzul Batchuluun、菊地 元史、屋代 隆
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 栃木県下野市
• [Presentation] Folliculostellate cells interach with microvessel mural cell ‘pericyte’ to maintain collagen arrangement ib rat anterior pituitary development of rat (2013)
  • Author(s): Takehiro Tukada, Ken Fujiwara, Dini Ramadhai, Tom KOUKI, Motoshi Kikuchi and Takashi Yashiro
  • Organizer: The Endocrine Society’s 95th Annual Meeting & Expo
  • Place of Presentation: San Francisco
• [Presentation] ラット下垂体前葉における新規細胞種の発見-Desmin-immunopositive Perivascular Cell- (2013)
  • Author(s): 屋代 隆、Depicha Jindatip、Alimuddin Tofrizal、幸喜 富、東 森生、菊地 元史、堀口 幸太郎
  • Organizer: 日本下垂体研究会第28回学術集会
  • Place of Presentation: 岩手県花巻市
• [Presentation] ラット下垂体前葉におけるTGFB2の発現とその作用 (2013)
  • Author(s): 塚田 岳大、堀口 幸太郎、菊地 元史、屋代 隆
  • Organizer: 第38回目日本比較内分泌学会大会
  • Place of Presentation: 宮崎県宮崎市
• [Remarks]
  • URL: http://www.jichi.ac.jp/histology/
• [Remarks] 自治医科大学解剖組織
  • URL: http://www.jichi.ac.jp/histology/
• [Remarks] 自治医科大学 解剖学講座 組織学部門 研究テーマ
  • URL: http://www.jichi.ac.jp/histology