1. Academic Validation
  2. RNase 7 Inhibits Uropathogenic Escherichia coli-Induced Inflammation in Bladder Cells under a High-Glucose Environment by Regulating the JAK/STAT Signaling Pathway

RNase 7 Inhibits Uropathogenic Escherichia coli-Induced Inflammation in Bladder Cells under a High-Glucose Environment by Regulating the JAK/STAT Signaling Pathway

  • Int J Mol Sci. 2022 May 5;23(9):5156. doi: 10.3390/ijms23095156.
Chen-Hsun Ho 1 2 Pin-Wen Liao 2 3 4 Chia-Kwung Fan 5 6 Shih-Ping Liu 7 Po-Ching Cheng 5 6
Affiliations

Affiliations

  • 1 Division of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11101, Taiwan.
  • 2 School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan.
  • 3 Department of Neurology, Cathay General Hospital, Taipei 10630, Taiwan.
  • 4 Graduate Institute of Neural Regenerative Medicine, College of Medicine Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
  • 5 Department of Molecular Parasitology and Tropical Diseases, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 6 Center for International Tropical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
  • 7 Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei 10002, Taiwan.
Abstract

Antimicrobial Peptides (AMPs), which are natural Antibiotics, protect against pathogens invading the urinary tract. RNase 7 with antimicrobial properties has rapid and powerful suppressive effects against Gram-positive and Gram-negative Bacterial infections. However, its detailed Antibacterial mechanisms have not been fully determined. Here, we investigate whether RNase 7 had an impact on bladder cells under uropathogenic Escherichia coli (UPEC) Infection in a high-glucose environment using in vitro GFP-UPEC-infected bladder cell and PE-labeled TLR4, STAT1, and STAT3 models. We provide evidence of the suppressive effects of RNase 7 on UPEC Infection and UPEC-induced inflammatory responses by regulating the JAK/STAT signaling pathway using JAK Inhibitor and STAT Inhibitor blocking experiments. Pretreatment with different concentrations of RNase 7 for 24 h concentration-dependently suppressed UPEC invasion in bladder cells (5 μg/mL reducing 45%; 25 μg/mL reducing 60%). The expressions of TLR4, STAT1, and STAT3 were also downregulated in a concentration-dependent manner after RNase 7 pretreatment (5 μg/mL reducing 35%, 54% and 35%; 25 μg/mL reducing 60%, 75% and 64%, respectively). RNase 7-induced decrease in UPEC Infection in a high-glucose environment not only downregulated the expression of TLR4 protein and the JAK/STAT signaling pathway but also decreased UPEC-induced secretion of exogenous inflammatory IL-6 and IL-8 cytokines, although IL-8 levels increased in the 25 μg/mL RNase 7-treated group. Thus, inhibition of STAT affected pSTAT1, pSTAT3, and TLR4 expression, as well as proinflammatory IL-6 and IFN-γ expression. Notably, blocking JAK resulted in the rebound expression of related proteins, especially pSTAT1, TLR4, and IL-6. The present study showed the suppressive effects of RNase 7 on UPEC Infection and induced inflammation in bladder epithelial cells in a high-glucose environment. RNase 7 may be an anti-inflammatory and anti-infective mediator in bladder cells by downregulating the JAK/STAT signaling pathway and may be beneficial in treating cystitis in DM patients. These results will help clarify the correlation between AMP production and UTI, identify the relationship between urinary tract Infection and diabetes in UTI patients, and develop novel diagnostics or possible treatments targeting RNase 7.

Keywords

JAK/STAT signaling pathway; RNase 7; antimicrobial peptide; inflammatory responses; urinary tract infection; uropathogenic Escherichia coli.

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