Details of a Researcher - NISHIYAMA Koichi

A new perfusion culture method with a self-organized capillary network Reviewed

Kei Sugihara, Yoshimi Yamaguchi, Shiori Usui, Yuji Nashimoto, Sanshiro Hanada, Etsuko Kiyokawa, Akiyoshi Uemura, Ryuji Yokokawa, Koichi Nishiyama, Takashi Miura

PLOS ONE 15 ( 10 October ) e0240552 - e0240552 2020.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Public Library of Science (PLoS)

DOI： 10.1371/journal.pone.0240552

RhoJ integrates attractive and repulsive cues in directional migration of endothelial cells Reviewed

Yoko Fukushima, Koichi Nishiyama, Hiroshi Kataoka, Marcus Fruttiger, Shigetomo Fukuhara, Kohji Nishida, Naoki Mochizuki, Hiroki Kurihara, Shin‐Ichi Nishikawa, Akiyoshi Uemura

The EMBO Journal 39 ( 12 ) e102930 2020.6

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.15252/embj.2019102930

Vascularized cancer on a chip: The effect of perfusion on growth and drug delivery of tumor spheroid Reviewed

Yuji Nashimoto, Ryu Okada, Sanshiro Hanada, Yuichiro Arima, Koichi Nishiyama, Takashi Miura, Ryuji Yokokawa

Biomaterials 229 119547 2020.1

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.biomaterials.2019.119547

Sex differences in the functional morphology of coronary arteries in embryonic mice. Reviewed International journal

Shion Nagasawa, Masami Kodama, Ryu Hagiwara, Kazuho Sakamoto, Koichi Nishiyama, Yuichiro Arima, Hiroki Kurihara, Junko Kurokawa

American journal of physiology. Heart and circulatory physiology 327 ( 6 ) H1390 - H1399 2024.12

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1152/ajpheart.00186.2024

Endothelial cells regulate alveolar morphogenesis by constructing basement membranes acting as a scaffold for myofibroblasts Reviewed

Watanabe-Takano H., Kato K., Oguri-Nakamura E., Ishii T., Kobayashi K., Murata T., Tsujikawa K., Miyata T., Kubota Y., Hanada Y., Nishiyama K., Watabe T., Fässler R., Ishii H., Mochizuki N., Fukuhara S.

Nature Communications 15 ( 1 ) 1622 2024.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Nature Communications

Alveologenesis is a spatially coordinated morphogenetic event, during which alveolar myofibroblasts surround the terminal sacs constructed by epithelial cells and endothelial cells (ECs), then contract to form secondary septa to generate alveoli in the lungs. Recent studies have demonstrated the important role of alveolar ECs in this morphogenetic event. However, the mechanisms underlying EC-mediated alveologenesis remain unknown. Herein, we show that ECs regulate alveologenesis by constructing basement membranes (BMs) acting as a scaffold for myofibroblasts to induce septa formation through activating mechanical signaling. Rap1, a small GTPase of the Ras superfamily, is known to stimulate integrin-mediated cell adhesions. EC-specific Rap1-deficient (Rap1iECKO) mice exhibit impaired septa formation and hypo-alveolarization due to the decreased mechanical signaling in myofibroblasts. In Rap1iECKO mice, ECs fail to stimulate integrin β1 to recruit Collagen type IV (Col-4) into BMs required for myofibroblast-mediated septa formation. Consistently, EC-specific integrin β1-deficient mice show hypo-alveolarization, defective mechanical signaling in myofibroblasts, and disorganized BMs. These data demonstrate that alveolar ECs promote integrin β1-mediated Col-4 recruitment in a Rap1-dependent manner, thereby constructing BMs acting as a scaffold for myofibroblasts to induce mechanical signal-mediated alveologenesis. Thus, this study unveils a mechanism of organ morphogenesis mediated by ECs through intrinsic functions.

DOI： 10.1038/s41467-024-45910-y

第1土曜特集 "かたちづくり" を制御する分子メカニズム形態形成と多細胞動態血管新生における血流による物理的力の役割

花田保之, 西山功一

医学のあゆみ 290 ( 1 ) 42 - 46 2024.7

Publishing type：Research paper (scientific journal) Publisher：医歯薬出版

DOI： 10.32118/ayu290010042

第5土曜特集血管･リンパ管研究の最前線と治療への展開血管研究のフロンティア再構成解析系を駆使した血流による血管新生の生体力学機序の解明

西山功一

医学のあゆみ 289 ( 13 ) 1093 - 1098 2024.6

Publishing type：Research paper (scientific journal) Publisher：医歯薬出版

DOI： 10.32118/ayu289131093

血管をとりまく力学環境による血管新生の制御

西山功一

生体医工学 Annual62 ( Abstract ) 95_2 - 95_2 2024

Authorship：Lead author,　Corresponding author Language：Japanese Publishing type：Part of collection (book) Publisher：公益社団法人日本生体医工学会

血管新生は、既存の血管から新たな血管が増生する反応である。個体発生期だけでなく成体においても、損傷した血管の修復や虚血状態の解除などの生理的な反応として生じる。逆にがんや炎症では、異常な血管を増生し、病態形成やその進展に関与する。我々はこれまで、血管新生で血管が効率よく増生するためには、血管新生因子VEGFなどの化学シグナルに刺激された血管内皮細胞が、集団として効率よく移動することが重要であることを明らかにした（Development, 2011; Cell Rep, 2015; EMBO J, 2020）。一方、新生した血管にはすぐに管腔構造が形成され血流が流れこむため、血流による力学刺激に常に晒されている。しかし、この血流刺激が、化学シグナルと相まってどのように血管新生制御に関与しているのか、ほとんどわかっていない。この点において我々は、血流によって生じる血管壁の伸展が、血管内皮細胞の移動を抑制することで血管新生による血管の伸長を負に制御する、新たな力学シグナルであることを報告した（Nat Commun, 2022）。　本セッションでは、最近さらに見出した血管新生の新たな生体力学的制御機構を紹介する。そこでは、血管内皮細胞の周囲に存在するもう一つの血管細胞ペリサイトが、血管周囲基質を硬くすることで血管内腔の拡張性を調節し、血流による血管新生抑制作用をさらに制御することで血管の増生を促進していた。

DOI： 10.11239/jsmbe.annual62.95_2

Rap1 small GTPase is essential for maintaining pulmonary endothelial barrier function in mice. Reviewed International journal

Kiyotake Yamamoto, Haruko Watanabe-Takano, Eri Oguri-Nakamura, Hitomi Matsuno, Daiki Horikami, Tomohiro Ishii, Ryuji Ohashi, Yoshiaki Kubota, Koichi Nishiyama, Takahisa Murata, Naoki Mochizuki, Shigetomo Fukuhara

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 37 ( 12 ) e23310 2023.12

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1096/fj.202300830RR

VEGF-NFAT-ダウン症因子-1シグナル軸を介した血管内皮分化や血管分岐制御機構の解明

亀井竣輔, 福嶋葉子, 植村明嘉, 有馬勇一郎, 西山功一, 南敬

脈管学 63 ( 1 ) 14 - 14 2023.2

Language：Japanese Publishing type：Part of collection (book) Publisher：(一社)日本脈管学会

特集新組織学シリーズⅢ:血管とリンパ管 Ⅰ.血管･リンパ管研究の多様なアプローチ In vitro再構成モデルを用いた血管新生における血流力学作用の解析

西山功一

生体の科学 73 ( 6 ) 517 - 522 2022.12

Publishing type：Research paper (scientific journal) Publisher：株式会社医学書院

DOI： 10.11477/mf.2425201609

Pericytes and shear stress each alter the shape of a self-assembled vascular network

Kazuya Fujimoto, Scott Erickson, Masamune Nakayama, Hroki Ihara, Kei Sugihara, Yuji Nashimoto, Koichi Nishiyama, Takashi Miura, Ryuji Yokokawa

Lab on a Chip 23 ( 2 ) 306 - 317 2022.12

Language：English Publishing type：Research paper (other academic)

DOI： 10.1039/d2lc00605g

VEGF-NFAT-ダウン症因子-1シグナル軸を介した血管分岐制御機構の解明

亀井竣輔, 福嶋葉子, 植村明嘉, 有馬勇一郎, 西山功一, 南敬

日本生化学会大会プログラム・講演要旨集 95回 3T12a - 06 2022.11

Language：Japanese Publishing type：Part of collection (book) Publisher：(公社)日本生化学会

ペリサイトによる血管周囲基質の力学的性質変化を介した血管新生促進機構

春田望智, 花田保之, 市川朝永, 尾関有香, 宮崎紬, 徐宇卿, 有馬勇一郎, 植村明嘉, 白木幸彦, 西山功一

日本生化学会大会プログラム・講演要旨集 95回 2T10a - 09 2022.11

Authorship：Lead author,　Last author,　Corresponding author Language：Japanese Publishing type：Research paper (other academic) Publisher：(公社)日本生化学会

Tumor microenvironmental 15-PGDH depletion promotes fibrotic tumor formation and angiogenesis in pancreatic cancer. Reviewed International journal

Luke Bu, Atsuko Yonemura, N Yasuda-Yoshihara, Tomoyuki Uchihara, Galym Ismagulov, Sanae Takasugi, Tadahito Yasuda, Yuya Okamoto, Fumimasa Kitamura, Takahiko Akiyama, Kota Arima, Rumi Itoyama, Jun Zhang, Lingfeng Fu, Xichen Hu, Feng Wei, Yuichiro Arima, Toshiro Moroishi, Koichi Nishiyama, Guojun Sheng, Toshifumi Mukunoki, Jun Otani, Hideo Baba, Takatsugu Ishimoto

Cancer science 113 ( 10 ) 3579 - 3592 2022.10

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1111/cas.15495

NFAT indicates nucleocytoplasmic damped oscillation via its feedback modulator Reviewed

Masashi Muramatsu, Takeshi Ito, Hokuto Shimoji, Miko Komiya, Yuri Miyamura, Koichi Nishiyama, Takashi Suzuki, Takashi Minami

Biochemical and Biophysical Research Communications 571 201 - 209 2021.9

Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.bbrc.2021.07.072

心駆出率が保持されている肥満関連心不全患者において内因性のケトン体は心保護作用を発揮する(Endogenous ketone bodies have cardioprotective effects in obesity related heart failure with preserved ejection fraction)

山田敏寛, 石田俊史, 徐宇卿, 高潮征爾, 花谷信介, 荒木智, 中村太志, 山本英一郎, 松下健一, 西山功一, 有馬勇一郎, 辻田賢一

日本心臓病学会学術集会抄録 69回 YIA1 - 4 2021.9

Language：Japanese Publishing type：Research paper (other academic) Publisher：(一社)日本心臓病学会

Dysregulation of Amphiregulin stimulates the pathogenesis of cystic lymphangioma Reviewed International coauthorship

Yoshida N., Yamamoto S., Hamashima T., Okuno N., Okita N., Horikawa S., Hayashi M., Dang T.C., Nguyen Q.L., Nishiyama K., Makinod T., Ishii Y., Tomihara K., Shimizu T., Shibuya M., Noguchi M., Sasahara M.

Proceedings of the National Academy of Sciences of the United States of America 118 ( 19 ) 2021.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Proceedings of the National Academy of Sciences of the United States of America

Along with blood vessels, lymphatic vessels play an important role in the circulation of body fluid and recruitment of immune cells. Postnatal lymphangiogenesis commonly occurs from preexisting lymphatic vessels by sprouting, which is induced by lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C). However, the key signals and cell types that stimulate pathological lymphangiogenesis, such as human cystic lymphangioma, are less well known. Here, we found that mouse dermal fibroblasts that infiltrate to sponges subcutaneously implanted express VEGF-D and sushi, Von Willebrand factor type A, EGF, and pentraxin domain containing 1 (SVEP1) in response to PDGFRβ signal. In vitro, Pdgfrb knockout (β-KO) fibroblasts had reduced expression of VEGF-D and SVEP1 and overproduced Amphiregulin. Dysregulation of these three factors was involved in the cyst-like and uneven distribution of lymphatic vessels observed in the β-KO mice. Similarly, in human cystic lymphangioma, which is one of the intractable diseases and mostly occurs in childhood, fibroblasts surrounding cystic lymphatics highly expressed Amphiregulin. Moreover, fibroblastderived Amphiregulin could induce the expression of Amphiregulin in lymphatic endothelial cells. The dual source of Amphiregulin activated EGFR expressed on the lymphatic endothelial cells. This exacerbation cascade induced proliferation of lymphatic endothelial cells to form cystic lymphangioma. Ultimately, excessive Amphiregulin produced by fibroblasts surrounding lymphatics and by lymphatic endothelial cells per se results in pathogenesis of cystic lymphangioma and will be a fascinating therapeutic target of cystic lymphangioma.

DOI： 10.1073/pnas.2019580118

Murine neonatal ketogenesis preserves mitochondrial energetics by preventing protein hyperacetylation Reviewed

Yuichiro Arima, Yoshiko Nakagawa, Toru Takeo, Toshifumi Ishida, Toshihiro Yamada, Shinjiro Hino, Mitsuyoshi Nakao, Sanshiro Hanada, Terumasa Umemoto, Toshio Suda, Tetsushi Sakuma, Takashi Yamamoto, Takehisa Watanabe, Katsuya Nagaoka, Yasuhito Tanaka, Yumiko K. Kawamura, Kazuo Tonami, Hiroki Kurihara, Yoshifumi Sato, Kazuya Yamagata, Taishi Nakamura, Satoshi Araki, Eiichiro Yamamoto, Yasuhiro Izumiya, Kenji Sakamoto, Koichi Kaikita, Kenichi Matsushita, Koichi Nishiyama, Naomi Nakagata, Kenichi Tsujita

Nature Metabolism 3 ( 2 ) 196 - 210 2021.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

DOI： 10.1038/s42255-021-00342-6