High-mobility group protein N2 induces autophagy by activating AMPK/ULK1 pathway and thereby boosts UPEC proliferation within bladder epithelial cells.

Abstract

Urinary tract infection is one of the most common bacterial infections which is mainly caused by Escherichia coli (UPEC). Autophagy plays a key role in immune response to eliminate invading pathogens. Exploring the effect of autophagy on UPEC infection and the molecular mechanisms will be benefit for the treatment of urinary tract infection. High-mobility group protein N2 (HMGN2), a highly conserved nuclear protein and an antibacterial peptide, has been associated with bacterial infection induced immune response; however, whether this function is due to the regulation of autophagy remains unclear. In this study, we demonstrate for the first time that HMGN2 is upregulated in UPEC infection of bladder epithelial cell line 5637 (BEC 5637). Furthermore, HMGN2 enhances autophagy in BEC 5637 via activation of AMPK and ULK1, whereas UPEC suppresses autophagy. In addition, the enhanced autophagy activity by HMGN2 overexpression or rapamycin boosts the proliferation of UPEC J96 in BEC 5637. In summary, our data indicate that HMGN2 activates autophagy via AMPK/ULK1 pathway which can be utilized by UPEC J96 for their proliferation within bladder epithelial cells.

• Authors: Fumei Zhang, Feimei Zhu, Jinhao Yang, Wen Zhang, Keyun Liu, Laibin Ren, Feng Xiong, Kefeng Lu, Dongze Li, Rui Zeng, Xiaoying Wang, Jingyu Li, Shanze Chen, Yi Wang, Junli Chen, Ning Huang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 513 Issue 1 Pg. 193-200 (05 21 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 30952427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• HMGN2 Protein
• Autophagy-Related Protein-1 Homolog
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Autophagy
• Autophagy-Related Protein-1 Homolog (metabolism)
• Cell Line
• Cell Proliferation
• Epithelial Cells (cytology, metabolism, microbiology)
• Escherichia coli (growth & development, metabolism)
• Escherichia coli Infections (metabolism, microbiology)
• Female
• HMGN2 Protein (metabolism)
• Humans
• Mice, Inbred C57BL
• Signal Transduction
• Urinary Bladder (cytology, metabolism, microbiology)
• Urinary Tract Infections (metabolism, microbiology)