Transforming growth factor-beta 1 disrupts angiogenesis during the follicular-luteal transition through the Smad-serpin family E member 1 (SERPINE1)/serpin family B member 5 (SERPINB5) signalling pathway in the cow

文献类型： 外文期刊

第一作者： Yan, Leyan

作者： Yan, Leyan;Qu, Xiaolu;Yu, Jianning;Shi, Zhendan;Yan, Leyan;Qu, Xiaolu;Yu, Jianning;Shi, Zhendan;Robinson, Robert S.;Woad, Kathryn J.

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关键词： angiogenesis; luteinisation; serpin family B member 5 (SERPINB5); serpin family E member 1 (SERPINE1); Smad; transforming growth factor-beta 1 (TGFB1)

期刊名称：REPRODUCTION FERTILITY AND DEVELOPMENT （ 影响因子：1.718； 五年影响因子：1.923 ）

ISSN： 1031-3613

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收录情况： SCI

摘要： Intense angiogenesis is critical for the development of the corpus luteum and is tightly regulated by numerous factors. However, the exact role transforming growth factor-beta 1 (TGFB1) plays during this follicular-luteal transition remains unclear. This study hypothesised that TGFB1, acting through TGFB receptor 1 (TGFBR1) and Smad2/3 signalling, would suppress angiogenesis during the follicular-luteal transition. Using a serum-free luteinising follicular angiogenesis culture system, TGFB1 (1 and 10 ngmL(-1)) markedly disrupted the formation of capillary-like structures, reducing the endothelial cell network area and the number of branch points (P<0.001 compared with control). Furthermore, TGFB1 activated canonical Smad signalling and inhibited endothelial nitric oxide synthase (NOS3) mRNA expression, but upregulated latent TGFB-binding protein and TGFBR1, serpin family E member 1 (SERPINE1) and serpin family B member 5 (SERPINB5) mRNA expression. SB431542, a TGFBR1 inhibitor, reversed the TGFB1-induced upregulation of SERPINE1 and SERPINB5. In addition, TGFB1 reduced progesterone synthesis by decreasing the expression of steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1) and 3b-hydroxysteroid dehydrogenase (HSD3B1) expression. These results show that TGFB1 regulates NOS3, SERPINE1 and SERPINB5 expression via TGFBR1 and Smad2/3 signalling and this could be the mechanism by which TGFB1 suppresses endothelial networks. Thereby, TGFB1 may provide critical homeostatic control of angiogenesis during the follicular-luteal transition. The findings of this study reveal the molecular mechanisms underlying the actions of TGFB1 in early luteinisation, which may lead to novel therapeutic strategies to reverse luteal inadequacy.

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