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International journal of molecular medicine

Knockdown of HMGN2 increases the internalization of Klebsiellaxa0pneumoniae by respiratory epithelial cells through the regulation of α5β1 integrin expression.


PMID 27460641

Abstract

Integrin receptors, a large family of adhesion receptors, are involved in the attachment of Klebsiellaxa0pneumoniae to respiratory epithelial cells, and subsequently cause the internalization of K.xa0pneumoniae 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 domainxa02xa0(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 α5β1xa0integrin in A549 cells. Therefore, we hypothesized that intercellular HMGN2 may mediate the internalization of K.xa0pneumoniae by altering the expression of α5β1xa0integrin. Using the A549 cell line, we demonstrated that HMGN2 knockdown induced the increased expression of α5β1xa0integrin on cell membranes, which resulted in a significant increase in K.xa0pneumoniae internalization. Further results revealed that HMGN2 silencing induced the expression of talin and the activation of α5β1xa0integrin, 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.xa0pneumoniae infection.

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