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

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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.
Publisher
WILEY
Issue Date
2017-06
Language
English
Article Type
Article
Keywords

ENDOTHELIAL-GROWTH-FACTOR; METASTATIC COLORECTAL-CANCER; GENE-EXPRESSION; PHENOTYPIC HETEROGENEITY; GRAVES-DISEASE; BLOOD-VESSELS; UP-REGULATION; TREATED RATS; ANTI-VEGF; IN-VITRO

Citation

EMBO MOLECULAR MEDICINE, v.9, no.6, pp.750 - 769

ISSN
1757-4676
DOI
10.15252/emmm.201607341
URI
http://hdl.handle.net/10203/224730
Appears in Collection
NT-Journal Papers(저널논문)MSE-Journal Papers(저널논문)
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