Role of the planar cell polarity pathway in regulating ectopic hair cell-like cells induced by Math1 and testosterone treatment
Role of the planar cell polarity pathway in regulating ectopic hair cell-like cells induced by Math1 and testosterone treatment
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平面细胞极性途径在调节 Math1 和睾酮治疗诱导的异位毛细胞样细胞中的作用。
DOI：
10.1016/j.brainres.2015.04.017
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发表时间：
2015-07
期刊：
影响因子：
2.9
通讯作者：
Chi, Fang-lu
中科院分区：
文献类型：
--
作者：
Han, Zhao;Cong, Ning;Ren, Dong-dong;Chi, Fang-lu
平面细胞极性(PCP)信号调节内耳感觉毛细胞的方向，调节耳蜗区的伸展。逆转录病毒介导的Math1转录因子的导入导致一些成熟的支持细胞转分化为毛细胞。睾酮是一种性腺性类固醇激素，在中枢神经系统(CNS)发育中与神经保护和再生有关。用Ad5-EGFP-Math1/Ad5-Math1体外培养新生小鼠耳蜗组织。在小上皮脊(LER)内建立异位毛细胞样细胞(HCLC)极性的方法，观察用或不用睾酮-3-(O-羧甲基)肟牛血清白蛋白(Teststerone-BSA)处理的情况，以确定PCP通路在Math1和睾酮处理诱导异位再生(HCLC)中的作用。Math1感染后，在LER中检测到新的异位再生的HCLC。当肝细胞形成富含肌动蛋白的立体纤毛后，基底体由中心向远端移动。此外，较窄的无感觉LER区域意味着在转染Math1后也建立了会聚延伸(CE)。在体外睾酮-BSA处理9天后，在LER中观察到更多的EDU(+)、SOX2(+)和HCLC细胞，并伴随着E-钙粘素的下调。有趣的是，Ad5-EGFP-Math1处理的LER的CE发生了改变，但HCLC的固有细胞极性没有明显改变。综上所述，我们的结果表明PCP信号参与了异位肝细胞癌的发展，并且异位感觉区的CE被睾酮-BSA通过下调细胞-细胞黏附而改变。睾酮-BSA和Math1处理可通过增殖和转分化促进LER中HCLCs的增加。
Planar cell polarity (PCP) signaling regulates cochlear extension and coordinates orientation of sensory hair cells in the inner ear. Retroviral-mediated introduction of the Math1 transcription factor leads to the transdifferentiation of some mature supporting cells into hair cells. Testosterone, a gonadal sex steroid hormone, is associated with neuroprotection and regeneration in Central Nervous System (CNS) development. Experiments were performedin vitrousing Ad5-EGFP-Math1/Ad5-Math1 in neonatal mouse cochleas. Establishment of ectopic hair-cell like cell(HCLC) polarity in the lesser epithelial ridge (LER) with or without testosterone-3-(O-carboxymethyl) oxime bovine serum albumin (testosterone-BSA) treatment was investigated to determine the role of the PCP pathway in regulating ectopic regenerated (HCLCs) through induction by Math1 and testosterone treatment. After Math1 infection, new ectopic regenerated HCLCs were detected in the LER. After the HCLCs developed actin-rich stereocilia, the basal bodies moved from the center to the distal side. Moreover, the narrower, non-sensory LER region meant that the convergent extension (CE) was also established after transfection with Math1. After 9 days ofin vitrotestosterone-BSA treatment, more Edu(+), Sox2(+), and HCLC cells were observed in the LER with an accompanying downregulation of E-cadherin. Interestingly, the CE of the Ad5-EGFP-math1 treated LER is altered, but the intrinsic cellular polarity of the HCLCs is not obviously changed. In summary, our results indicate that PCP signaling is involved in the development of ectopic HCLCs and the CE of the ectopic sensory region is altered by testosterone-BSA through downregulation of cell–cell adhesion. Testosterone-BSA and Math1 treatment could promote an increase in HCLCs in the LER through proliferation and transdifferentiation.
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影响因子：
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