Published online Jan 21, 2024. doi: 10.3748/wjg.v30.i3.252
Peer-review started: August 31, 2023
First decision: October 29, 2023
Revised: November 8, 2023
Accepted: December 18, 2023
Article in press: December 18, 2023
Published online: January 21, 2024
Processing time: 139 Days and 20 Hours
Ulcerative colitis (UC) is an inflammatory condition associated with frequent relapse and recurrence. Dysregulation of intestinal epithelial cells (IECs) and mucosal barrier impairment contribute to sustained inflammation in UC. Hence, an in-depth exploration of the triggers and mechanisms of IEC death could result in efficacious therapeutic options for UC patients.
Evidence suggests the involvement of SLC6A14 in UC pathogenesis, but the central regulator remains unknown.
We aimed to explore the role of SLC6A14 in UC-associated pyroptosis.
Quantitative real-time polymerase chain reaction (qRT-PCR), immunoblotting, and IHC assessed SLC6A14 in human UC tissues. LPS induced FHC and NCM460 cell inflammation, modeling enteritis; SLC6A14 levels were assessed. Pyroptosis markers were quantified using enzyme-linked immunosorbent assay, Western blotting, and qRT-PCR, while EdU incubation, CCK-8 assay and flow cytometry examined proliferation and apoptosis, respectively. Mouse models of UC were used for verification.
SLC6A14 was elevated, correlating with NLRP3 in UC tissues. LPS-induced FHC and NCM460 cells showed increased SLC6A14. Reduced SLC6A14 boosted cell proliferation, suppressed apoptosis. Lower SLC6A14 Led to decreased pyroptosis-associated proteins (ASC, IL-1β, IL-18, NLRP3). NLRP3 overexpression counteracted sh-SLC6A14 effects on LPS-induced FHC and NCM460 cell pyroptosis. SLC6A14 improved murine dextran sulfate sodium colitis mucosa.
SLC6A14 promotes UC pyroptosis via NLRP3 upregulation, indicating therapeutic potential through SLC6A14/NLRP3 axis modulation.
We demonstrated the close involvement of SLC6A14 in promoting pyroptosis in the context of UC by upregulating NLRP3 expression. These findings underline the potential significance of targeting the SLC6A14/NLRP3 axis-mediated pyroptosis as a promising therapeutic strategy for addressing UC.