Keratinocyte growth factor (KGF) induces podosome formation via integrin-Erk1/2 signaling in human immortalized oral epithelial cells
Keratinocyte growth factor (KGF) induces podosome formation via integrin-Erk1/2 signaling in human immortalized oral epithelial cells
复制标题
角质形成细胞生长因子 (KGF) 通过整合素-Erk1/2 信号在人永生化口腔上皮细胞中诱导足体形成
DOI：
10.1016/j.cellsig.2019.05.007
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发表时间：
2019-09-01
影响因子：
4.8
通讯作者：
He, Sangang
中科院分区：
文献类型：
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作者：
Sa, Guoliang;Liu, Zhikang;He, Sangang
最近的研究确定了整合素在角质形成细胞生长因子（KGF）诱导的口腔上皮粘附和网栓延长中的作用。然而，如何细胞外基质（ECM）重塑合作与增加上皮细胞粘附在网栓延长尚未确定。Podosomes是细胞-基质接触结构，其联合收割机结合多种能力，包括粘附和基质降解。在本研究中，我们确定了KGF治疗后，在人永生化口腔上皮细胞（HIOECs）的腹侧形成的足状体。此外，包括整合素α 6、β 4、α 3、β 1和MMP 14在内的足体组分与F-肌动蛋白-皮质蛋白复合物共定位，基质降解试验证明了F-肌动蛋白-皮质蛋白复合物降解基质的能力。用特异性阻断抗体抑制整联蛋白亚基β 4和β 1以及抑制Erk 1/2可消除KGF诱导的podosome形成。值得注意的是，用特异性小干扰RNA（siRNA）敲低整联蛋白亚基β 4和β 1下调Erk 1/2的磷酸化水平。相反，抑制Erk 1/2可以上调整合素亚基β 4和β 1的表达。这些结果表明，KGF通过整合素-Erk 1/2信号转导诱导HIOECs中的podosome形成，提示整合素增强口腔上皮粘附和网栓伸长的新机制。
Recent study established the role of integrins in keratinocyte growth factor (KGF)-induced oral epithelial adhesion and rete peg elongation. However, how extracellular matrix (ECM) remodeling cooperates with the increased epithelial adhesion during rete peg elongation has yet to be determined. Podosomes are cell-matrix contact structures that combine several abilities, including adhesion and matrix degradation. In the present study, we identified podosome formation at the ventral side of human immortalized oral epithelial cells (HIOECs) upon KGF treatment. Moreover, podosomal components including integrin alpha 6, beta 4, alpha 3, beta 1 and MMP14 colocalized with the F-actin-cortactin complex and matrix degradation assays demonstrated the ability of the F-actin-cortactin complex to degrade matrix. Inhibition both of integrin subunits beta 4 and beta 1 with specific blocking antibodies and inhibition of Erk1/2 abrogated the KGF-induced podosome formation. Notably, knockdown of integrin subunits beta 4 and beta 1 with specific small interfering RNA (siRNA) downregulated the phosphorylation levels of Erk1/2. In contrast, inhibition of both Erk1/2 could upregulate the expression of integrin subunits beta 4 and beta 1. These results demonstrate that KGF induces podosome formation via integrin-Erk1/2 signaling in HIOECs, suggesting a novel mechanism by which integrins enhance oral epithelial adhesion and rete peg elongation.