Vitamin D regulating TGF-β induced epithelial-mesenchymal transition.
Vitamin D regulating TGF-β induced epithelial-mesenchymal transition.
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DOI：
10.1186/s12931-014-0146-6
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发表时间：
2014-11-21
影响因子：
5.8
通讯作者：
Agrawal DK
中科院分区：
文献类型：
--
作者：
Fischer KD;Agrawal DK
上皮下纤维化是哮喘患者气道重塑的典型标志。转化生长因子β(转化生长因子-β)是一种重要的纤维化调节因子，可通过诱导上皮细胞-间充质转化来诱导上皮细胞的气道重塑。维生素D具有免疫调节功能，但其对控制上皮下纤维化的作用尚不清楚。将人支气管上皮细胞(BEAS-2B)暴露于骨化三醇后，用转化生长因子-β-1或转化生长因子-β-2刺激BEAS-2B，用Western印迹和定量聚合酶链式反应分析E-钙粘素、蜗牛、波形蛋白和N-钙粘蛋白的蛋白表达和转录水平。采用侵袭实验和划痕损伤实验鉴定细胞在处理后的迁移特性。转化生长因子-β-1降低E-钙粘蛋白的表达，增加Snail、Vimentin和N-钙粘蛋白的蛋白表达和转录，增加细胞的侵袭和迁移。骨化三醇可减弱转化生长因子-β-1和转化生长因子-β-2诱导的细胞运动。骨化三醇可抑制转化生长因子β-1诱导的人呼吸道上皮细胞上皮细胞的迁移和侵袭，而骨化三醇对转化生长因子-β-2的影响较小。而维生素D在上皮-间充质转化过程中的调节作用对转化生长因子-β-1诱导的转化更为有效。因此，骨化三醇可能在预防和治疗上皮下纤维化和气道重塑方面具有潜在的治疗作用。
Subepithelial fibrosis is a characteristic hallmark of airway remodeling in asthma. A critical regulator of fibrosis, transforming growth factor β (TGF-β), can induce airway remodeling in epithelial cells through induction of epithelial-mesenchymal transition (EMT). Vitamin D has immunomodulatory functions, however, its effect on controlling subepithelial fibrosis is not known. Human bronchial epithelial cells (BEAS-2B) were exposed to calcitriol followed by stimulation with TGF-β1 or TGF-β2. The protein expression and mRNA transcripts for E-cadherin, Snail, vimentin, and N-cadherin were analyzed by Western blot and qPCR. An invasion assay and scratch wound assay were performed to identify the migratory properties of the cells following treatments. TGF-β1 decreased E-cadherin expression and increased protein expression and mRNA transcripts of Snail, vimentin, and N-cadherin together with increased cell invasion and migration. TGF-β2 elicited migratory response similar to TGF-β1 but induced the expression of EMT markers differently from that by TGF-β1. Calcitriol attenuated TGF-β1- and TGF-β2-induced cell motility. Also, calcitriol inhibited the expression of EMT markers in TGF-β1-treated epithelial cells with less effect on TGF-β2. These data suggest that calcitriol inhibits both migration and invasion induced by TGF-β1 and TGF-β2 in human airway epithelial cells. However, the regulatory effect of vitamin D in epithelial-mesenchymal transition was more effective to TGF-β1-induced changes. Thus, calcitriol could be a potential therapeutic agent in the prevention and management of subepithelial fibrosis and airway remodeling.
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DOI：
10.1111/cea.12102
发表时间：
2013-06
期刊：
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子：
--
作者：
Agrawal T;Gupta GK;Agrawal DK
通讯作者：
Agrawal DK
DOI：
10.1165/ajrcmb.10.5.8179909
发表时间：
1994-05-01
影响因子：
6.4
作者：
BRADDING, P;ROBERTS, JA;HOLGATE, ST
通讯作者：
HOLGATE, ST
影响因子：
3.2
作者：
Berraies A;Hamzaoui K;Hamzaoui A
通讯作者：
Hamzaoui A
影响因子：
6.1
作者：
Batra, V;Musani, AI;Peters, SP
通讯作者：
Peters, SP
影响因子：
9.1
作者：
Agrawal, Tanupriya;Gupta, Gaurav K.;Agrawal, Devendra K.
通讯作者：
Agrawal, Devendra K.