Treatment with all-trans-retinoic acid decreases levels of endogenous TGF-β1 in time mesenchyme of the developing mouse inner ear
Treatment with all-trans-retinoic acid decreases levels of endogenous TGF-β1 in time mesenchyme of the developing mouse inner ear
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DOI：
10.1002/(sici)1096-9926(200004)61:4
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发表时间：
2000-04-01
期刊：
影响因子：
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通讯作者：
Liu, W
中科院分区：
文献类型：
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作者：
Frenz, DA;Liu, W
背景：先前的研究表明，小鼠胚胎在子宫内暴露于高剂量的全反式维甲酸（atRA）会导致发育中的内耳及其周围软骨囊的缺陷，而培养的骨膜间充质和耳部上皮暴露于高剂量的外源性atRA会抑制耳部囊的软骨形成。方法：在本研究中，我们研究了atRA暴露对内源性转化生长因子- β (1) （tgf - β(1)）表达的影响，tgf - β(1)是一种介导上皮-间质相互作用的信号分子，指导内耳包膜的发育。结果：我们的研究结果表明，与对照标本相比，暴露于atra的E10.5和E12日龄胚胎的周期间质中tgf - β(1)的免疫染色明显减少。与这些体内研究结果一致，高密度培养的E10.5骨膜间充质+耳部上皮，与未处理的对照培养的tgf - β(1)水平相比，经抑制软骨形成的atRA剂量处理后，tgf - β(1)水平显著降低。此外，我们证明了通过补充过量的tgf - β 1培养物，可以拯救培养的骨膜间充质和耳上皮，使其免受atra诱导的软骨抑制。结论：我们的研究结果支持了tgf - β(1)在内耳发育过程中atRA致畸机制中发挥作用的假设。(C) 2000 Wiley-Liss, Inc。
Background: Previous studies have shown that in utero exposure of the mouse embryo to high doses of all-trans-retinoic acid (atRA) produces defects of the developing inner ear and its surrounding cartilaginous capsule, while exposure of cultured periotic mesenchyme plus otic epithelium to high doses of exogenous atRA results in an inhibition of otic capsule chondrogenesis.Methods: In this study, we examine the effects of atRA exposure on the endogenous expression of transforming growth factor-beta(1) (TGF-beta(1)), a signaling molecule that mediates the epithelial-mesenchymal interactions that guide the development of the capsule of the inner ear.Results: Our results demonstrate a marked reduction in immunostaining for TGF-beta(1) in the periotic mesenchyme of atRA-exposed embryos of age E10.5 and E12 days in comparison with control specimens. Consistent with these in vivo findings, high-density cultures of E10.5 periotic mesenchyme plus otic epithelium, treated with doses of atRA that suppress chondrogenesis, showed significantly decreased levels of TGF-beta(1), as compared with TGF-beta(1) levels in untreated control cultures. Furthermore, we demonstrate a rescue of cultured periotic mesenchyme plus otic epithelium from atRA-induced chondrogenic suppression by supplementation of cultures with excess TGF-beta 1.Conclusions: Our results support the hypothesis that TGF-beta(1) plays a role in mechanisms of atRA teratogenicity during inner ear development. (C) 2000 Wiley-Liss, Inc.