Effect of canonical NF-κB signaling pathway on the differentiation of rat dental epithelial stem cells
Effect of canonical NF-κB signaling pathway on the differentiation of rat dental epithelial stem cells
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经典NF-κB信号通路对大鼠牙上皮干细胞分化的影响
DOI：
10.1186/s13287-019-1252-7
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发表时间：
2019-05-20
影响因子：
7.5
通讯作者：
Tian, Weidong
中科院分区：
文献类型：
--
作者：
Liang, Yan;Chen, Guoqing;Tian, Weidong
背景资料：核因子-κ B（NF-κ B B）是一种重要的转录因子，参与了包括牙齿发育在内的生长、分化、器官形成、凋亡、炎症、免疫反应等多种生理和病理过程。然而，NF-κ B B是否参与了大鼠切牙中牙上皮干细胞（DESCs）的调控尚不清楚。在此，我们研究了经典NF-κ B信号通路在DESC中的特异性分化调控机制，并提供了参与DESC分化的串扰机制。加入NF-κ B信号通路的激活剂或抑制剂后，采用Western blot和实时荧光定量PCR方法检测釉质形成相关基因、蛋白和典型转化生长因子β（TGF β）的表达（TGF-β）信号传导。此外，我们在体外通过向成釉诱导培养基中分别加入NF-κ B信号通路的激活剂或抑制剂来进行成釉诱导。结果：在NF-κ B激活的DESCs中，成釉相关基因和蛋白的表达以及TGF-β信号通路均被下调，而SMAD 7的表达则被上调。此外，NF-κ B抑制的DESC表现出与NF-κ B激活的DESC相反的结果。结论：经典NF-κ B信号通路通过上调SMAD 7的表达进而抑制经典TGF-β-SMAD信号通路参与了DESC的分化调控。
Background: Nuclear factor-kappa B (NF-kappa B), an important transcription factor, participates in many physiological and pathological processes such as growth, differentiation, organogenesis, apoptosis, inflammation, and immune response, including tooth development. However, it is still unknown whether NF-kappa B participates in the regulation of dental epithelial stem cells (DESCs) in postnatal rat incisors. Here, we investigated the specific differentiation regulatory mechanisms of the canonical NF-kappa B signaling pathway in DESCs and provided the mechanism of cross-talk involved in DESC differentiation.Methods: After adding the activator or inhibitor of the NF-kappa B signaling pathway, Western blot and quantitative real-time PCR were used to analyze the expressions of amelogenesis-related genes and proteins and canonical transforming growth factor-beta (TGF-beta) signaling. In addition, we used amelogenesis induction in vitro by adding the activator or inhibitor of the NF-kappa B signaling pathway to the amelogenesis-induction medium, respectively. Recombinant TGF-beta was used to activate the TGF-beta pathway, and SMAD7 siRNA was used to downregulate the expression of SMAD7 in DESCs.Results: We found that the expression of amelogenesis-related genes and proteins as well as TGF-beta signaling were downregulated, while SMAD7 expression was increased in NF-kappa B-activated DESCs. In addition, NF-kappa B-inhibited DESCs exhibited opposite results compared with NF-kappa B-activated DESCs. Furthermore, the canonical NF-kappa B signaling pathway suppressed the canonical TGF-beta-SMAD signaling by inducing SMAD7 expression involved in the regulation of DESC differentiation.Conclusions: These results indicate that the canonical NF-kappa B signaling pathway participated in the regulation of DESC differentiation, which was through upregulating SMAD7 expression and further suppressing the canonical TGF-beta-SMAD signaling pathway.