Research Paper Volume 15, Issue 10 pp 4363—4373
PCSK6 mediates Th1 differentiation and promotes chronic colitis progression and mucosal barrier injury via STAT1
- 1 Department of Surgery, Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, People’s Republic of China
- 2 Department of Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, People’s Republic of China
Received: February 8, 2023 Accepted: May 1, 2023 Published: May 20, 2023
https://doi.org/10.18632/aging.204739How to Cite
Copyright: © 2023 Mei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
This study was aimed at investigating the expression and role of proprotein convertase subtilisin/kexin type (PCSK6) in inflammatory bowel disease (IBD). DSS induced mouse colitis and mucosal barrier injury, down-regulation of TJ proteins, improvement of permeability, and increases of the proportions of Th1 and M1 macrophages. After PCSK6 knockdown, the colitis in KO mice was improved relative to WT mice, the TJ protein levels increased, and the proportions of Th1 and M1 macrophages decreased. STAT1 inhibitor treatment also inhibited chronic colitis in mice. As revealed by in-vitro experiments, PCSK6 overexpression promoted the transformation of Th0 into Th1, while PCSK6 silencing suppressed the transfection. COPI assay results revealed the presence of targeted binding relation between PCSK6 and STAT1.
PCSK6 binds to STAT1 to promote STAT1 phosphorylation and regulate Th1 cell differentiation, thus promoting the M1 polarization of macrophages and aggravating colitis progression. PCSK6 is promising as the new target for the treatment of colitis.