Open AccessVEGFR2 but not VEGFR3 governs integrity and remodeling of thyroid angiofollicular unit in normal state and during goitrogenesis
Author(s) -
Jang Jeon Yeob,
Choi Sung Yong,
Park Intae,
Park Do Young,
Choe Kibaek,
Kim Pilhan,
Kim Young Keum,
Lee ByungJoo,
Hirashima Masanori,
Kubota Yoshiaki,
Park JeongWon,
Cheng SheueYann,
Nagy Andras,
Park Young Joo,
Alitalo Kari,
Shong Minho,
Koh Gou Young
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201607341
Subject(s) - thyroid , angiopoietin receptor , mural cell , vascular endothelial growth factor , biology , medicine , endocrinology , pathology , angiogenesis , vegf receptors , vascular smooth muscle , smooth muscle
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 VEGFR 2 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 VEGFR 2, but not VEGFR 3, is indispensable for maintenance of thyroid vascular integrity. Notably, blockade of VEGF ‐A or VEGFR 2 not only abrogated vascular remodeling but also inhibited follicular hypertrophy, which led to the reduction of thyroid weights during goitrogenesis. Importantly, VEGFR 2 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 ‐A–vascular VEGFR 2 axis as a main regulator for thyrotropin‐dependent thyroid angiofollicular remodeling and goitrogenesis.