Transforming growth factor Beta2 is required for valve remodeling during heart development.
Transforming growth factor Beta2 is required for valve remodeling during heart development.
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DOI：
10.1002/dvdy.22702
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发表时间：
2011-09
影响因子：
2.5
通讯作者：
Doetschman, Thomas
中科院分区：
文献类型：
--
作者：
Azhar, Mohamad;Brown, Kristen;Gard, Connie;Chen, Hwudaurw;Rajan, Sudarsan;Elliott, David A.;Stevens, Mark V.;Camenisch, Todd D.;Conway, Simon J.;Doetschman, Thomas
尽管转化生长因子β2（TGFβ2）在上皮间质转化（EMT）中的功能已得到充分研究，但其在瓣膜重塑中的作用仍有待充分探索。在这里，我们使用组织学、形态测量、免疫组织化学和分子方法，结果表明主要细胞外基质 (ECM) 成分的显着失调导致 Tgfb2-/- 胚胎中的瓣膜重塑缺陷。数据表明，Tgfb2-/- 胚胎中的垫间充质细胞分化受损。 Tgfb2-/- 胚胎的增生瓣膜中透明质酸和软骨连接蛋白-1 (CRTL1) 增加，表明心脏发育过程中垫间充质向软骨细胞谱系的扩张和多样化增加。最后，蛋白质印迹和免疫组织化学分析表明，在瓣膜重塑过程中，Tgfb2-/- 胚胎中 SMAD2/3 的激活减少。总的来说，数据表明，TGFβ2 在心脏发育过程中通过诱导基质组织和抑制垫间充质分化为软骨细胞谱系来促进瓣膜重塑和分化。
Although the function of transforming growth factor beta2 (TGFβ2) in epithelial mesenchymal transition (EMT) is well studied, its role in valve remodeling remains to be fully explored. Here, we used histological, morphometric, immunohistochemical and molecular approaches and showed that significant dysregulation of major extracellular matrix (ECM) components contributed to valve remodeling defects in Tgfb2-/- embryos. The data indicated that cushion mesenchymal cell differentiation was impaired in Tgfb2-/- embryos. Hyaluronan and cartilage link protein-1 (CRTL1) were increased in hyperplastic valves of Tgfb2-/- embryos, indicating increased expansion and diversification of cushion mesenchyme into the cartilage cell lineage during heart development. Finally, western blot and immunohistochemistry analyses indicate that the activation of SMAD2/3 was decreased in Tgfb2-/- embryos during valve remodeling. Collectively, the data indicate that TGFβ2 promotes valve remodeling and differentiation by inducing matrix organization and suppressing cushion mesenchyme differentiation into cartilage cell lineage during heart development.
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影响因子：
20.1
作者：
Egorova AD;Khedoe PP;Goumans MJ;Yoder BK;Nauli SM;ten Dijke P;Poelmann RE;Hierck BP
通讯作者：
Hierck BP
影响因子：
2.5
作者：
Azhar, Mohamad;Runyan, Raymond B.;Gard, Connie;Sanford, L. Philip;Miller, Marian L.;Andringa, Anastasia;Pawlowski, Sharon;Rajan, Sudarsan;Doetschman, Thomas
通讯作者：
Doetschman, Thomas
影响因子：
30.8
作者：
Gitler, AD;Zhu, Y;Epstein, JA
通讯作者：
Epstein, JA
DOI：
10.1073/pnas.0711067105
发表时间：
2008-02-19
影响因子：
11.1
作者：
Elliott, David A.;McIntosh, Michael T.;Joiner, Keith A.
通讯作者：
Joiner, Keith A.
影响因子：
4.6
作者：
Jian, B;Narula, N;Levy, RJ
通讯作者：
Levy, RJ