Establishment of region-specificity in glomerular endothelial cells

• Project/Area Number: 18K08221
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Aino University
• Principal Investigator: KURIHARA Hidetake 藍野大学, 医療保健学部, 教授 (80311976)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 血管内皮細胞 / 膜ドメイン / 腎臓 / メサンギウム細胞 / 腎炎 / 肺 / ペリサイト

Outline of Final Research Achievements

The glomerular capillaries responsible for glomerular filtration are surrounded by two cells. One is a podocyte, which forms a specialized filter called a slit diaphragm to filtrate blood. The other is a mesangial cell, which regulates the diameter of capillary and control blood flow. We found that glomerular capillaries have two large domain structures and express different molecules depending on the type of surrounding cells. The study demonstrates that it is possible to clarify the fact that endothelial cells constituting one capillary are not uniform and change their properties in various way according to the surrounding environment and are involved in tissue-specific functions.

Academic Significance and Societal Importance of the Research Achievements

肺の毛細血管や腎臓の糸球体毛細血管はそれぞれ、呼吸と血液の濾過による尿生成という生体にとって極めて重要な働きをしている。毛細血管を構成する内皮細胞は一様な構造をしているように考えられているが、本研究により、内皮細胞は血管を取り巻く細胞や細胞外基質の状況に対応して形態や発現する分子を変化させる証拠を見いだした。この研究により、毛細血管は周囲を取り巻く環境に応じて性質を変化させることができる可塑性に富む構造であることが分かった。この血管内皮細胞の性質を分子レベルで明らかにすることにより、それぞれの組織において循環系が果たす役割をさらに詳細に理解することができるようになる

Research Products

• [Journal Article] Manipulation of nephron-patterning signals enables selective induction of podocytes from human pluripotent stem cells. (2019)
  • Author(s): Yoshimura Y, Taguchi A, Tanigawa S, Yatsuda J, Kamba T, Takahashi S, Kurihara H, Mukoyama M, Nishinakamura R.
  • Journal Title: Journal of the American Society of Nephrology Volume: 30 Issue: 2 Pages: 304-321
  • DOI: 10.1681/asn.2018070747
  • Peer Reviewed
• [Journal Article] KIF11 as a Potential Marker of Spermatogenesis Within Mouse Seminiferous Tubule Cross-sections (2019)
  • Author(s): Miki Hara-Yokoyama, Hidetake Kurihara, Shozo Ichinose, Hironori Matsuda, Shizuko Ichinose, Masaru Kurosawa, Norihiro Tada, Chihiro Iwahara, Kazue Terasawa, Katarzyna A Podyma-Inoue, Koichi Furukawa , Kazuhisa Iwabuchi
  • Journal Title: Journal of Histochemistry & Cytochemistry Volume: 67 Issue: 11 Pages: 813-824
  • DOI: 10.1369/0022155419871027
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] UNC119 is a binding partner of tumor suppressor Ras-association domain family 6 and induces apoptosis and cell cycle arrest by MDM2 and p53 (2018)
  • Author(s): Iwasa Hiroaki、Sarkar Aradhan、Shimizu Takanobu、Sawada Takeru、Hossain Shakhawoat、Xu Xiaoyin、Maruyama Junichi、Arimoto-Matsuzaki Kyoko、Withanage Kanchanamala、Nakagawa Kentaro、Kurihara Hidetake、Kuroyanagi Hidehito、Hata Yutaka
  • Journal Title: Cancer Science Volume: 109 Issue: 9 Pages: 2767-2780
  • DOI: 10.1111/cas.13706
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Organoids from nephrotic disease-derived iPSCs identify impaired NEPHRIN localization and slit diaphragm formation in kidney podocytes. (2018)
  • Author(s): Tanigawa S, Islam M, Naganuma H, Yoshimura Y, Miike K, Sharmin S, Haque F, Era T, Nakazato H, Nakanishi K, Sakuma T, Yamamoto T, Kurihara H, Taguchi A, Nishinakamura R
  • Journal Title: Stem Cell Rep Volume: 11 Issue: 3 Pages: 1-14
  • DOI: 10.1016/j.stemcr.2018.08.003
  • NAID: 120006847306
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Rac1/PAK1シグナルの活性化は腎糸球体上皮細胞の突起形成を阻害する (2021)
  • Author(s): 斉藤康二，與川正治, 水田さり，多田奏絵, 小田萌紀, 栗原秀剛，太田安隆
  • Organizer: 第94回日本生化学会大会
• [Presentation] PAR3 Restricts the Expansion of Neural Precursor Cells by Regulating Hedgehog Signaling. (2021)
  • Author(s): Hirose T,Sugitani Y, Kurihara H, Kazama H, Kusaka C, Noda T, Takahashi H,Ohno S
  • Organizer: 第44回日本分子生物学会年会
• [Presentation] FilGAP controls cell-extracellular matrix adhesion in kidney podocytes. (2021)
  • Author(s): Yokawa S, Saito K, Hatakeyama H, Takahashi N, Kurihara H, Ohta Y
  • Organizer: 第44回日本分子生物学会年会
• [Presentation] Renal Lesions Associated with MYH9 Disorder (5773delG Mutation): Clinical and Pathological Analyses. (2019)
  • Author(s): Yoshikawa K, Kunishima S, Kurihara H, Takahashi K, Nakaya I, Soma J
  • Organizer: Am Soc Nephrol
  • Int'l Joint Research
• [Presentation] 腎糸球体内皮細胞の場に応じた領域特異性について (2019)
  • Author(s): 栗原秀剛
  • Organizer: 第51回日本臨床分子形態学会総会・学術集会
• [Presentation] Altered expression of acetylated tubulin in enteric neurons in Hirschsprung disease mouse model. (2018)
  • Author(s): 宮原克、田中奈々、藤原なほ、栗原秀剛、山高篤行
  • Organizer: 第107回日本病理学会総会
• [Presentation] 腎糸球体上皮細胞の突起形成におけるRacGAP因子FilGAPの機能解析 (2018)
  • Author(s): 斉藤康二、水田さり、多田奏絵、栗原秀剛、太田安隆
  • Organizer: 第91回日本生化学会大会
• [Book] ジュンケイラ組織学 第5版 (2018)
  • Author(s): 栗原秀剛
  • Total Pages: 608
  • Publisher: 丸善