Conditional expression of the dominant-negative TGF-β receptor type II elicits lingual epithelial hyperplasia in transgenic mice.
Conditional expression of the dominant-negative TGF-β receptor type II elicits lingual epithelial hyperplasia in transgenic mice.
复制标题
显性失活 TGF-β 受体 II 型的条件表达引起转基因小鼠舌上皮增生。
DOI：
10.1002/dvdy.23933
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Zhou,Mingliang
中科院分区：
文献类型：
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作者：
Li,Feng;Zhou,Mingliang
研究背景转化生长因子-β(Transform Growth For-β，TGFR)信号转导通路被认为是一种强有力的细胞增殖抑制因子。然而，许多缺乏必需的Tgfbr2基因的上皮细胞仍然维持着正常的组织动态平衡。结果在K14+细胞中缺乏转化生长因子-β信号转导通路的小鼠，舌尖腹面发生侵袭性癌，舌背表面丝状乳头呈现不同程度的病理改变。此外，在转化生长因子-β信号阻断后，舌上皮细胞中组蛋白H4和组蛋白H3的乙酰化水平迅速增加，pMAPK活性增强，Jagged2失活。结论我们的结果有助于理解转化生长因子-β信号在舌上皮细胞动态平衡和癌变过程中的调控作用。©2013 Wiley期刊，Inc.
BackgroundThe transforming growth factor‐β (TGF‐β) signaling pathway is generally believed to be a potent inhibitor of proliferation. However, many epithelia lacking the essentialTgfbr2gene still maintain normal tissue homeostasis. Here, transgenic mice expressingrtTAfrom the humankeratin 14(K14) promoter were used to generate an inducible dominant‐negative TGF‐β receptor type II (Tgfbr2) mutant model, which allowed us to distinguish between the primary and secondary effects of TGF‐β signaling disruption by Doxycycline treatment in K14+ epithelial stem cells.ResultsWe showed that in mice lacking TGF‐β signaling in K14+ cells, invasive carcinomas developed on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface showed different pathological changes from the tip to the posterior of the tongue. In addition, acetylation levels of histone H4 and histone H3 rapidly increased, while pMAPK activity was enhanced and Jagged2 inactivated in lingual epithelia after disruption of TGF‐β signaling.ConclusionsOur results contribute to the understanding of TGF‐β signaling in regulating homeostasis and carcinogenesis in lingual epithelia.Developmental Dynamics 242:444–455, 2013. © 2013 Wiley Periodicals, Inc.