Knockdown of HMGN2 increases the internalization of Klebsiella pneumoniae by respiratory epithelial cells through the regulation of α5β1 integrin expression.
Knockdown of HMGN2 increases the internalization of Klebsiella pneumoniae by respiratory epithelial cells through the regulation of α5β1 integrin expression.
复制标题
HMGN2 的敲低通过调节 α5β1 整合素表达增加呼吸道上皮细胞对肺炎克雷伯菌的内化
DOI：
10.3892/ijmm.2016.2690
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发表时间：
2016-09
影响因子：
5.4
通讯作者：
Huang N
中科院分区：
文献类型：
--
作者：
Wang X;Li J;Chen S;Shen X;Yang X;Teng Y;Deng L;Wang Y;Chen J;Wang X;Huang N
整合素受体是粘附受体的一个大家族，参与肺炎克雷伯菌与呼吸道上皮细胞的粘附，并随后引起K.宿主细胞引起的肺炎。尽管已经报道了许多分子调节呼吸道上皮细胞中整合素受体的表达和活性，但具体的潜在分子机制仍然很大程度上未知。高迁移率族核小体结合结构域2（HMGN 2）是一种非组蛋白核蛋白，在真核细胞中普遍存在。我们前期的研究表明HMGN 2在脂多糖诱导的A549细胞中影响染色质功能并调节抗菌肽的表达，这表明HMGN 2在天然免疫应答中起着关键作用。此外，我们的cDNA微阵列分析表明，HMGN 2敲低诱导A549细胞中α5β1整合素的表达增强。因此，我们推测细胞间HMGN 2可能介导K.通过改变α5β1整联蛋白的表达，使用A549细胞系，我们证明HMGN 2敲低诱导细胞膜上α5β1整合素表达增加，这导致K.肺炎内化进一步的研究结果表明，HMGN 2沉默可诱导talin的表达和α5β1整合素的活化，从而导致FAK和Src磷酸化后肌动蛋白聚合。这项研究表明，通过靶向HMGN 2来治疗K.肺炎感染。
Integrin receptors, a large family of adhesion receptors, are involved in the attachment of Klebsiella pneumoniae to respiratory epithelial cells, and subsequently cause the internalization of K. pneumoniae by host cells. Although a number of molecules have been reported to regulate the expression and activity of integrin receptors in respiratory epithelial cells, the specific underlying molecular mechanisms remain largely unknown. High mobility group nucleosomal binding domain 2 (HMGN2), a non-histone nuclear protein, is present in eukaryotic cells as a ubiquitous nuclear protein. Our previous studies have demonstrated that HMGN2 affects chromatin function and modulates the expression of antibacterial peptide in A549 cells exposed to lipopolysaccharide, which indicates the critical role of HMGN2 in innate immune responses. In addition, our cDNA microarray analysis suggested that HMGN2 knockdown induced the enhanced expression of α5β1 integrin in A549 cells. Therefore, we hypothesized that intercellular HMGN2 may mediate the internalization of K. pneumoniae by altering the expression of α5β1 integrin. Using the A549 cell line, we demonstrated that HMGN2 knockdown induced the increased expression of α5β1 integrin on cell membranes, which resulted in a significant increase in K. pneumoniae internalization. Further results revealed that HMGN2 silencing induced the expression of talin and the activation of α5β1 integrin, which led to actin polymerization following the phosphorylation of FAK and Src. This study suggests a possible therapeutic application for bacterial internalization by targeting HMGN2 in order to treat K. pneumoniae infection.