Arecoline suppresses epithelial cell viability by upregulating tropomyosin-1 through the transforming growth factor-β/Smad pathway.
Arecoline suppresses epithelial cell viability by upregulating tropomyosin-1 through the transforming growth factor-β/Smad pathway.
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DOI：
10.1080/13880209.2020.1851729
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发表时间：
2020-11-18
影响因子：
3.8
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Li L;Gu L;Yao Z;Wang Y;Tang Z;Wu X
口腔黏膜下纤维化（OSF）是一种慢性进行性疾病。槟榔中的槟榔碱被认为是一个重要的致病因素。然而，其潜在机制尚不清楚。本研究旨在阐明槟榔碱对HaCaT细胞原肌球蛋白-1 （tropomyosin-1, TPM1）的表达及其调控机制。HaCaT细胞分为三组：(1)对照组；(2)槟榔碱（0.16 mM）处理48 h(3)槟榔碱（0.16 mM）处理后，用小干扰RNA （siRNA）转染TPM1 (50 nM) 48 h。进行CCK8、细胞周期和凋亡表型分析。采用PCR和western blot方法检测TPM1的表达水平，并对其信号通路进行检测。槟榔碱的IC50约为50 μg/mL （0.21 mM）。槟榔碱剂量（0.16 mM）和时间（48 h）显著增加HaCaT细胞中TPM1 mRNA和蛋白水平的表达。槟榔碱抑制HaCaT细胞生长，使细胞周期阻滞在G1期，诱导细胞凋亡。sirna介导的TPM1敲低可减弱槟榔碱对G1期细胞增殖、凋亡和细胞周期阻滞的影响。此外，SB431542阻断转化生长因子(TGF)-β受体可显著抑制槟榔碱处理细胞中TPM1的表达。槟榔碱通过TGF-β/Smad信号通路上调TPM1抑制HaCaT细胞活力。本研究为进一步研究槟榔碱和TPM1在OSF中的作用提供了科学依据，并可推广到更广泛的药理学研究。TPM1可能是治疗OSF的一个有前景的分子靶点。
Oral submucous fibrosis (OSF) is a chronic and progressive disease. Arecoline, present in betel nuts, has been proposed as a vital aetiological factor. However, the underlying mechanism remains unclear. This research elucidates the expression of tropomyosin-1 (TPM1) and its regulation mechanism in HaCaT cells treated with arecoline. HaCaT cells were assigned into three groups: (1) Control; (2) Treated with arecoline (0.16 mM) for 48 h (3) Treated with arecoline (0.16 mM) and transfected with small interfering RNA (siRNA) for TPM1 (50 nM) for 48 h. CCK8, cell cycle, and apoptosis phenotypic analyses were performed. PCR and western blot analyses were performed to detect the expression level of TPM1 and examine the related signalling pathway. The IC50 of arecoline was approximately 50 μg/mL (0.21 mM). The arecoline dose (0.16 mM) and time (48 h) markedly increased TPM1 expression at the mRNA and protein levels in HaCaT cells. Arecoline suppressed the cell growth, caused cell cycle arrest at the G1 phase, and induced cell apoptosis in HaCaT cells. siRNA-mediated knockdown of TPM1 attenuated the effect of arecoline on cell proliferation, apoptosis, and cell cycle arrest at the G1 phase. Furthermore, blocking of the transforming growth factor (TGF)-β receptor using SB431542 significantly suppressed TPM1 expression in the cells treated with arecoline. Arecoline suppresses HaCaT cell viability by upregulating TPM1 through the TGF-β/Smad signalling pathway. This research provides a scientific basis for further study of arecoline and TPM1 in OSF and can be generalised to broader pharmacological studies. TPM1 may be a promising molecular target for treating OSF.
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DOI：
10.1083/jcb.201109045
发表时间：
2012-03-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gervasi M;Bianchi-Smiraglia A;Cummings M;Zheng Q;Wang D;Liu S;Bakin AV
通讯作者：
Bakin AV
影响因子：
5.3
作者：
Kubo E;Hasanova N;Fatma N;Sasaki H;Singh DP
通讯作者：
Singh DP
DOI：
10.4103/0973-029x.131902
发表时间：
2014-01-01
期刊：
Journal of oral and maxillofacial pathology : JOMFP
影响因子：
--
作者：
Hosthor, Sreelatha S;Mahesh, Pushpalatha;Chitra, S
通讯作者：
Chitra, S
影响因子：
3.2
作者：
Huang, J. L.;Lu, H. H.;Lin, C. S.
通讯作者：
Lin, C. S.
DOI：
10.1016/s1079-2104(96)80404-5
发表时间：
1996-02-01
影响因子：
--
作者：
Le, PV;Gornitsky, M
通讯作者：
Gornitsky, M