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Abstract：
BACKGROUND: 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.
OBJECTIVE: To explore the role of SLC6A14 in UC-associated pyroptosis.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: SLC6A14 promotes UC pyroptosis by regulating NLRP3, suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.
OBJECTIVE: To explore the role of SLC6A14 in UC-associated pyroptosis.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: SLC6A14 promotes UC pyroptosis by regulating NLRP3, suggesting the therapeutic potential of modulating the SLC6A14/NLRP3 axis.
摘要：
背景：溃疡性结肠炎（UC）是一种经常复发和复发的炎症性疾病。有证据表明SLC6A14参与UC发病机制，但是中央监管机构仍然未知。
目的：探讨SLC6A14在UC相关细胞凋亡中的作用。
方法：定量实时聚合酶链反应（qRT-PCR），免疫印迹,和免疫组织化学用于评估人UC组织中的SLC6A14。脂多糖（LPS）用于诱导FHC和NCM460细胞的炎症和模型肠炎，和SLC6A14水平进行评估。使用酶联免疫吸附测定对焦亡标志物进行定量，西方印迹,和qRT-PCR，和EdU孵化，CCK-8测定和流式细胞术用于检测增殖和凋亡。UC的小鼠模型用于验证。
结果：UC组织中SLC6A14升高并与NLRP3相关。LPS诱导的FHC和NCM460细胞显示增加的SLC6A14水平。减少SLC6A14可增加细胞增殖并抑制细胞凋亡。减少SLC6A14减少焦亡相关蛋白(ASC，IL-1β,IL-18，NLRP3）。NLRP3过表达抵消了sh-SLC6A14对LPS诱导的FHC和NCM460细胞焦亡的影响。SLC6A14改善葡聚糖硫酸钠诱导的结肠炎小鼠的粘膜。
结论：SLC6A14通过调节NLRP3促进UC细胞凋亡，提示调节SLC6A14/NLRP3轴具有治疗潜力。
目的：探讨SLC6A14在UC相关细胞凋亡中的作用。
方法：定量实时聚合酶链反应（qRT-PCR），免疫印迹,和免疫组织化学用于评估人UC组织中的SLC6A14。脂多糖（LPS）用于诱导FHC和NCM460细胞的炎症和模型肠炎，和SLC6A14水平进行评估。使用酶联免疫吸附测定对焦亡标志物进行定量，西方印迹,和qRT-PCR，和EdU孵化，CCK-8测定和流式细胞术用于检测增殖和凋亡。UC的小鼠模型用于验证。
结果：UC组织中SLC6A14升高并与NLRP3相关。LPS诱导的FHC和NCM460细胞显示增加的SLC6A14水平。减少SLC6A14可增加细胞增殖并抑制细胞凋亡。减少SLC6A14减少焦亡相关蛋白(ASC，IL-1β,IL-18，NLRP3）。NLRP3过表达抵消了sh-SLC6A14对LPS诱导的FHC和NCM460细胞焦亡的影响。SLC6A14改善葡聚糖硫酸钠诱导的结肠炎小鼠的粘膜。
结论：SLC6A14通过调节NLRP3促进UC细胞凋亡，提示调节SLC6A14/NLRP3轴具有治疗潜力。
