生存ダイナミクス研究センター

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA)

血管マトリクス生物学（柳沢 裕美）
Vascular Matrix
matrix Biology
biology (YANAGISAWA Hiromi)
YANAGISAWA Hiromi, M.D. Ph.D. , Professor
Professor
Life Science Center for Survival Dynamics, TARA
Life
Science
Center for Survival Dynamics, TARA
E-mailaddress:hkyanagisawa@tara.tsukuba.ac.jp
E-mail address:hkyanagisawa@tara.tsukuba.ac.jp
YAMASHIRO Yoshito, Ph.D., Assistant Professor
YoshitoYamashiro,
Ph.D.
E-mail address:
yamayoshito@tara.tsukuba.ac.jp
Assistant
Professor(VascularGroupLeader)
KIMURA Kenichi, Ph.D.,
Assistant
Professor
E-mailaddress:kkimura@tara.tsukuba.ac.jp
yamayoshito@tara.tsukuba.ac.jp
Email address:
https://www.saggymousehkytsukuba.com/
URL: http://saggymouse.tara.tsukuba.ac.jp

血管メカノトランスダクション機構の解明と疾患への応用
血管は心拍出による機械的刺激に常に晒されています。ではいかに機械的刺激が、血管細胞（内皮細胞、平滑筋細胞、線維芽細胞）に伝搬され、生化学シグナルに変換されるのでしょうか？解剖学的に異なる血管や、老化や炎症で性状が変化した血管では、シグナル伝達はどのように変わるのでしょうか？私たちは、大動脈瘤や大動脈解離、血管内膜肥厚、加齢性動脈硬化などのモデルマウスを作製し、達はどのように変わるのでしょうか？私たちは、循環器疾患(大動脈瘤や加齢性動脈硬化)のモデルマウスと、ストレッチアッセイ・ラ
ストレッチアッセイ・ライブイメージング・ゲノムエディティングなどの技術を組み合わせ、メカノトランスダクション機構の解明とイブイメージング・ゲノムエディティングなどの技術を組み合わせ、メカノトランスダクション機構の解明と診断や治療への応用に取その破綻によっておこる疾患の診断や治療標的の探求に取り組んでいます。バイオエンジニアリング・ラマンイメージング・バイオマ
り組んでいます。バイオエンジニアリング・ラマンイメージング・バイオマテリアル・心臓血管外科などの研究室との共同研究も進めテリアル・心臓血管外科などの研究室との共同研究も進めています。ています。

Elucidating the molecular mechanism of mechanotransduction inblood vessels and its application to vascular diseases
Blood vessels are constantly exposed to thepumpingof theHowever,1) how
vascularcells
the mechanicalmechanical stressstress caused
caused byby cyclic
the cyclic
pumpingofheart.
the heart.
However:1) howvascular(endothelial
cells,cells,smoothmusclecells,andandfibroblasts)sense
biochemicalcells (endothelialsmoothmusclecells,fibroblasts)
sensestressstressandandconvert
convert toit tobiochemicalsignals,
signals,2)2)whether
whether anatomicallyanatomicallydifferent
signaling
pathway(s), and 3)
how damaged/aged
extracellular extracellularmatrix of the matrix
vessels affects
affects
different vascularvascularsystems
systemshave
havedistinct
distinctmechanotransduction
pathways,3) how damaged/aged
modelsmodels
of cardiovasculardiseasessuch asaortic
aneurysms
andmechanotransduction,
are largely
We utilize
intracellular signaling pathways,areunknown.
largely unknown.
Wemouseutilize mouseof cardiovasculardiseasessuch
as aortic
aneurysm,
elucidatethe molecularmechanisminjury
of mechanotransductionin thevesselassay,
wall bycombining
vitro
stretch assays,
live imaging,aortic dissection,and mechanicaland combine in vitro
stretchflow
chamber,inlive
imaging,
and genome
editingand
togenome
We are currently
collaboratingwith bioengineering,
andareclinicallaboratories.
elucidateediting.
the molecularmechanismof mechanotransductionin the biomaterials,vessel wall. We
currently
collaborating with bioengineering,biomaterial, and clinical laboratories.

Molecular dissection
andaneurysmal
dissection of
ofmechanotransduction
mechanotransductionininnormal
normal(left)(left)
andaneurysmal
wall (right).
Mechanosensitive
molecules,
Egr1
andThbs1,
arehighly(right). The mechanosensitive transcription factor, Egr1, activates theupregulated inaneurysm.
angiotensin
II thesignaling
pathway and induces upregulation of Thbs1 in theLabel-free imaging of the aorta.

aneurysm wall.
Recent publications• Y. Yamashiro, et al. Abnormal mechanosensing and cofilin activation promote the progression of ascending aortic aneurysms in mice. ScienceSignaling. 8(399):ra105 (2015).
• Y. Yamashiro, B. Q. Thang, S. Shin, C. A. Lino et al. Role of thrombospondin-1 in mechanotransduction and development of thoracic aortic
aneurysm in mouse and humans. Circ. Res. 123(6):660-672 (2018)14