SLC6A14 promotes ulcerative colitis progression by facilitating NLRP3 inflammasome-mediated pyroptosis.

Abstract

Ulcerative colitis (UC) is an inflammatory condition with frequent relapse and recurrence. Evidence suggests the involvement of SLC6A14 in UC pathogenesis, but the central regulator remains unknown. To explore the role of SLC6A14 in UC-associated pyroptosis. Quantitative real-time polymerase chain reaction (qRT-PCR), immunoblotting, and immunohistochemical were used to assess SLC6A14 in human UC tissues. Lipopolysaccharide (LPS) was used to induce inflammation in FHC and NCM460 cells and model enteritis, and SLC6A14 levels were assessed. Pyroptosis markers were quantified using enzyme-linked immunosorbent assay, Western blotting, and qRT-PCR, and EdU incubation, CCK-8 assays and flow cytometry were used to examine proliferation and apoptosis. Mouse models of UC were used for verification. SLC6A14 was increased and correlated with NLRP3 in UC tissues. LPS-induced FHC and NCM460 cells showed increased SLC6A14 levels. Reducing SLC6A14 increased cell proliferation and suppressed apoptosis. Reducing SLC6A14 decreased pyroptosis-associated proteins (ASC, IL-1β, IL-18, NLRP3). NLRP3 overexpression counteracted the effects of sh-SLC6A14 on LPS-induced FHC and NCM460 cell pyroptosis. SLC6A14 improved the mucosa in mice with dextran sulfate sodium-induced colitis. SLC6A14 promotes UC pyroptosis by regulating NLRP3, suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.