VEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular unit in normal state and during goitrogenesis

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http://hdl.handle.net/10138/199200

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Jang , J Y , Choi , S Y , Park , I , Park , D Y , Choe , K , Kim , P , Kim , Y K , Lee , B-J , Hirashima , M , Kubota , Y , Park , J-W , Cheng , S-Y , Nagy , A , Park , Y J , Alitalo , K , Shong , M & Koh , G Y 2017 , ' VEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular unit in normal state and during goitrogenesis ' , EMBO molecular medicine , vol. 9 , no. 6 , pp. 750-769 . https://doi.org/10.15252/emmm.201607341

Title: VEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular unit in normal state and during goitrogenesis
Author: Jang, Jeon Yeob; Choi, Sung Yong; Park, Intae; Park, Do Young; Choe, Kibaek; Kim, Pilhan; Kim, Young Keum; Lee, Byung-Joo; Hirashima, Masanori; Kubota, Yoshiaki; Park, Jeong-Won; Cheng, Sheue-Yann; Nagy, Andras; Park, Young Joo; Alitalo, Kari; Shong, Minho; Koh, Gou Young
Contributor: University of Helsinki, Research Programs Unit
Date: 2017-06
Language: eng
Number of pages: 20
Belongs to series: EMBO molecular medicine
ISSN: 1757-4676
URI: http://hdl.handle.net/10138/199200
Abstract: Thyroid gland vasculature has a distinguishable characteristic of endothelial fenestrae, a critical component for proper molecular transport. However, the signaling pathway that critically governs the maintenance of thyroid vascular integrity, including endothelial fenestrae, is poorly understood. Here, we found profound and distinct expression of follicular epithelial VEGF-A and vascular VEGFR2 that were precisely regulated by circulating thyrotropin, while there were no meaningful expression of angiopoietin-Tie2 system in the thyroid gland. Our genetic depletion experiments revealed that VEGFR2, but not VEGFR3, is indispensable for maintenance of thyroid vascular integrity. Notably, blockade of VEGF-A or VEGFR2 not only abrogated vascular remodeling but also inhibited follicular hypertrophy, which led to the reduction of thyroid weights during goitrogenesis. Importantly, VEGFR2 blockade alone was sufficient to cause a reduction of endothelial fenestrae with decreases in thyrotropin-responsive genes in goitrogen-fed thyroids. Collectively, these findings establish follicular VEGF-Avascular VEGFR2 axis as a main regulator for thyrotropindependent thyroid angiofollicular remodeling and goitrogenesis.
Subject: thyroid angiofollicular unit
thyroid goitrogenesis
vascular remodeling
VEGFR2
ENDOTHELIAL-GROWTH-FACTOR
METASTATIC COLORECTAL-CANCER
GENE-EXPRESSION
PHENOTYPIC HETEROGENEITY
GRAVES-DISEASE
BLOOD-VESSELS
UP-REGULATION
TREATED RATS
ANTI-VEGF
IN-VITRO
3111 Biomedicine
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