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

Abstract

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.

• Authors: Xinyuan Wang, Jingyu Li, Shanze Chen, Xiaofei Shen, Xiaolong Yang, Yan Teng, Luxia Deng, Yi Wang, Junli Chen, Xiaoying Wang, Ning Huang
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 38 Issue 3 Pg. 737-46 (Sep 2016) ISSN: 1791-244X [Electronic] Greece
• PMID: 27460641 (Publication Type: Journal Article)

Chemical References

• Actins
• HMGN2 Protein
• Integrin alpha5beta1
• Focal Adhesion Kinase 1
• PTK2 protein, human
• Proto-Oncogene Proteins pp60(c-src)

Topics

• A549 Cells
• Actins (metabolism)
• Blotting, Western
• Cell Line
• Cell Line, Tumor
• Endocytosis (physiology)
• Epithelial Cells (metabolism, microbiology)
• Focal Adhesion Kinase 1 (metabolism)
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• HMGN2 Protein (genetics, metabolism)
• Humans
• Integrin alpha5beta1 (genetics, metabolism)
• Klebsiella pneumoniae (physiology)
• Microscopy, Fluorescence
• Phosphorylation
• Polymerization
• Proto-Oncogene Proteins pp60(c-src) (metabolism)
• RNA Interference
• Respiratory System (cytology)
• Reverse Transcriptase Polymerase Chain Reaction