It has been reported that high mobility group nucleosomal binding domain 2 (HMGN2) is a nucleus‐related protein that regulates gene transcription and plays a critical role in bacterial clearance. An elevated level of HMGN2 reduced integrin α5/β1 expression of human pulmonary epithelial A549 cells was demonstrated during Klebsiella pneumoniae infection, thus weakening bacterial adhesion and invasion. However, the mechanism by which HMGN2 regulates integrin expression remains unclear. This study found that a transcription factor‐nuclear factor I (NFI), which serves as the potential target of HMGN2 regulated integrin expression. The results showed that HMGN2 was able to promote NFIA and NFIB expression by increasing H3K27 acetylation of NFIA/B promoter regions. The integrin α5/β1 expression was significantly enhanced by knockdown of NFIA/B via a siRNA approach. Meanwhile, NFIA/B silence could also compromise the inhibition effect of HMGN2 on the integrin α5/β1 expression. Mechanistically, it was demonstrated that HMGN2 facilitated the recruitment of NFI on the promoter regions of integrin α5/β1 according to the chromatin immunoprecipitation assay. In addition, it was further demonstrated that the knockdown of NFIA/B induced more adhesion of Klebsiella pneumoniae on pulmonary epithelial A549 cells, which could be reversed by the application of an integrin inhibitor RGD. The results revealed a regulatory role of HMGN2 on the transcription level of integrin α5/β1, indicating a potential treatment strategy against Klebsiella pneumoniae‐induced infectious lung diseases.

中文翻译：

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高迁移率族核小体结合2通过I因子减少了整合素α5/β1介导的肺炎克雷伯菌在人肺上皮细胞上的粘附

据报道，高迁移率族核小体结合结构域2（HMGN2）是一种与核有关的蛋白，它调节基因转录并在细菌清除中起关键作用。肺炎克雷伯氏菌期间，HMGN2水平升高，降低了人肺上皮A549细胞的整合素α5/β1表达感染，从而削弱细菌的粘附和入侵。但是，HMGN2调节整联蛋白表达的机制仍不清楚。这项研究发现，转录因子-核因子I（NFI）作为HMGN2调控整联蛋白表达的潜在靶标。结果表明，HMGN2能够通过增加NFIA / B启动子区域的H3K27乙酰化来促进NFIA和NFIB表达。通过siRNA方法敲低NFIA / B，可显着增强整联蛋白α5/β1的表达。同时，NFIA / B沉默也可能损害HMGN2对整联蛋白α5/β1表达的抑制作用。从机制上讲，根据染色质免疫沉淀试验，HMGN2促进了NFI在整联蛋白α5/β1启动子区域的募集。此外，肺炎克雷伯菌对肺上皮A549细胞的作用可通过应用整联蛋白抑制剂RGD逆转。结果表明，HMGN2在整联蛋白α5/β1的转录水平上具有调节作用，表明针对肺炎克雷伯菌引起的传染性肺病的潜在治疗策略。