血管生成
尿道下裂
邻苯二甲酸二丁酯
体内
后代
生物
转录因子
男科
化学
细胞生物学
内科学
内分泌学
癌症研究
医学
生物化学
遗传学
基因
怀孕
有机化学
作者
Lei Wu,Fei Shi,Zhang Yong-qing,Xinyu Xu,Zhiwen Xie,Shan Hua,Shujie Xia,Juntao Jiang
标识
DOI:10.1016/j.ecoenv.2024.115941
摘要
Early exposure to dibutyl phthalate (DBP) can cause hypospadias in newborn foetuses. However, the underlying molecular mechanism is not well defined. Aberrant angiogenesis is associated with various dysplasias including urogenital deficits. In vivo and in vitro angiogenesis assays showed reduced angiogenesis in the hypospadias group and DBP exposed group. RNA-sequencing analysis of DBP-treated HUVECs revealed decreased expression of transforming growth factor beta 1-induced transcript 1 (TGFB1I1) and a significantly enriched angiogenesis-associated pathway. Further experiments revealed that decreased TGFB1I1 expression was associated with disrupted tube formation and migration, which resulted in decreased angiogenesis. Functional assays revealed that the overexpression of TGFB1I1 promoted tube formation and migration of HUVECs in the DBP-treated group. Moreover, we showed that the transcription factor AR was regulated by TGFB1I1 through inhibiting its translocation from the cytoplasm to the nucleus. Together, our results identified TGFB1I1 as a component of aberrant angiogenesis in hypospadias rats and its interaction with AR might be a potential target for hypospadias development.
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