Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan 650032, China.
School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China.
Eur J Cell Biol. 2022 Apr;101(2):151223. doi: 10.1016/j.ejcb.2022.151223. Epub 2022 Apr 4.
The abnormal differentiation of Th17 cells aggravates ulcerative colitis (UC). Antimicrobial peptides (AMPs) exert pivotal protection functions against UC. KT2 is a cationic AMP that mediates colon cancer development. However, KT2's function in UC remains unclear.
The UC mouse model was induced by administering 2.5% dextran sulfate sodium, and the mice were given an enema of KT2. KT2's function in UC and Th17 cell differentiation in vivo was evaluated through various molecular experiments. The KT2's function in Th17 cell differentiation in vitro was evaluated by the proportion of CD4 IL-17 T cells, IL-17 levels, and RORγt expression levels. Meanwhile, the mechanism was assessed through quantitative real-time PCR, various loss-of-function assays, and dual-luciferase reporter gene assay.
KT2 restrained Th17 cell differentiation in both in vivo and in vitro UC models and slowed the UC process. KT2 elevated miR-302c-5p expression, as well as restrained Th17 cell differentiation by increasing miR-302c-5p. Meanwhile, miR-302c-5p interacted with the signal transducer and activator of transcription 3 (STAT3) and negatively regulated its expression. Furthermore, our data revealed that KT2 restrained the activation of STAT3 by elevating miR-302c-5p, thereby inhibiting Th17 cell differentiation.
KT2 alleviates UC by repressing Th17 cell differentiation through the miR-302c-5p/STAT3 axis.
Th17 细胞的异常分化会加重溃疡性结肠炎（UC）。抗菌肽（AMPs）对 UC 具有重要的保护作用。KT2 是一种阳离子 AMP，介导结肠癌的发生。然而，KT2 在 UC 中的作用尚不清楚。
通过给予 2.5%葡聚糖硫酸钠诱导 UC 小鼠模型，并用 KT2 进行灌肠。通过各种分子实验评估 KT2 在 UC 和体内 Th17 细胞分化中的作用。通过 CD4 IL-17 T 细胞的比例、IL-17 水平和 RORγt 表达水平评估 KT2 在体外 Th17 细胞分化中的作用。同时，通过定量实时 PCR、各种功能丧失实验和双荧光素酶报告基因实验评估其机制。
KT2 抑制了体内和体外 UC 模型中的 Th17 细胞分化，并减缓了 UC 进程。KT2 增加了 miR-302c-5p 的表达，通过增加 miR-302c-5p 来抑制 Th17 细胞分化。同时，miR-302c-5p 与信号转导和转录激活因子 3（STAT3）相互作用，负调控其表达。此外，我们的数据表明，KT2 通过升高 miR-302c-5p 抑制 STAT3 的激活，从而抑制 Th17 细胞分化。
KT2 通过 miR-302c-5p/STAT3 轴抑制 Th17 细胞分化来缓解 UC。
