The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development.
The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development.
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DOI：
10.1007/s00441-012-1330-y
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发表时间：
2012-09
影响因子：
3.6
通讯作者：
Cupp, Andrea S.
中科院分区：
文献类型：
--
作者：
McFee, Renee M.;Rozell, Timothy G.;Cupp, Andrea S.
血管内皮生长因子A(VEGFA)因其在卵泡发育中的作用而被广泛研究，是一种重要的血管生成因子。由于随着卵泡大小的增加，卵泡膜层的血管化增加，VEGFA可能通过调节血管生成来影响卵泡的生长。然而，VEGFA也可能通过非血管生成机制影响卵泡的发育，因为它的表达定位于非血管卵泡和细胞。VEGFA基因八个外显子的mRNA选择性剪接导致各种VEGFA亚型的形成。每种异构体都有独特的性质，并由成熟蛋白质中的氨基酸数量来识别。促血管生成亚型(VEGFA_XXX)由外显子8a编码，而具有抗血管生成特性的姐妹亚型(VEGFA_XXXB)由外显子8b编码。在大多数组织中表达的VEGFA主要是抗血管生成的VEGFA_XXXB亚型，而促血管生成的VEGFA亚型在血管生成活跃的组织中表达上调。尽管现在可以区分促血管生成和抗血管生成亚型，但到目前为止，许多评估VEGFA在卵巢和卵泡发育中的研究都没有区分促血管生成VEGFA和抗血管生成VEGFA。我们实验室的实验表明，促血管生成的VEGFA促进卵泡的募集和早期的卵泡发育，而抗血管生成的VEGFA抑制这些过程。因此，促血管生成和抗血管生成的VEGFA亚型的平衡在卵泡发育过程中非常重要。需要进一步的研究来阐明这种平衡调节卵泡形成和进展的方式。
Vascular endothelial growth factor A (VEGFA) has been extensively studied because of its role in follicular development and is a principal angiogenic factor essential for angiogenesis. Since vascularization of the theca layer increases as follicles progress in size through preantral and antral stages, VEGFA might influence follicle growth via the regulation of angiogenesis. However, VEGFA might also influence follicular development through nonangiogenic mechanisms, since its expression has been localized in nonvascular follicles and cells. Alternative mRNA splicing of eight exons from the VEGFA gene results in the formation of various VEGFA isoforms. Each isoform has unique properties and is identified by the number of amino acids within the mature protein. Proangiogenic isoforms (VEGFA_XXX) are encoded by exon 8a, whereas a sister set of isoforms (VEGFA_XXXB) with antiangiogenic properties is encoded by exon 8b. The antiangiogenic VEGFA_XXXB isoforms comprise the majority of VEGFA expressed in most tissues, whereas expression of the proangiogenic VEGFA isoforms is upregulated in tissues undergoing active angiogenesis. Although proangiogenic and antiangiogenic isoforms can now be distinguished from one another, many studies evaluating VEGFA in ovarian and follicular development up to now have not differentiated proangiogenic VEGFA from antiangiogenic VEGFA. Experiments from our laboratory indicate that proangiogenic VEGFA promotes follicle recruitment and early follicular development and antiangiogenic VEGFA inhibits these processes. The balance of proangiogenic versus antiangiognic VEGFA isoforms is thus of importance during follicle development. Further studies are warranted to elucidate the way that this balance regulates follicular formation and progression.
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影响因子：
3.6
作者：
Artac, Robin A.;McFee, Renee M.;Cupp, Andrea S.
通讯作者：
Cupp, Andrea S.
影响因子：
3.6
作者：
Flaws, JA;Hirshfield, AN;Furth, PA
通讯作者：
Furth, PA
影响因子：
2.3
作者：
Celik-Ozenci, C;Akkoyunlu, G;Demir, R
通讯作者：
Demir, R
影响因子：
6.7
作者：
Brännström, M;Zackrisson, U;Bourne, T
通讯作者：
Bourne, T
影响因子：
56.9
作者：
DEVRIES, C;ESCOBEDO, JA;WILLIAMS, LT
通讯作者：
WILLIAMS, LT