机构:[1]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan 650032, China消化内科内科科室云南省消化疾病研究所省级研究所[2]School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, China
BACKGROUND: 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.
METHODS: 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 RORgammat expression levels. Meanwhile, the mechanism was assessed through quantitative real-time PCR, various loss-of-function assays, and dual-luciferase reporter gene assay.
RESULTS: 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.
CONCLUSION: KT2 alleviates UC by repressing Th17 cell differentiation through the miR-302c-5p/STAT3 axis.
基金:
This study was supported by Yunnan Health Training Project of High
Level Talents (H-2018040).
第一作者机构:[1]Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan 650032, China
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推荐引用方式(GB/T 7714):
Dandan Gu,Qiong Nan,Yinglei Miao,et al.KT2 alleviates ulcerative colitis by reducing Th17 cell differentiation through the miR-302c-5p/STAT3 axis[J].European journal of cell biology.2022,101(2):151223.doi:10.1016/j.ejcb.2022.151223.
APA:
Dandan Gu,Qiong Nan,Yinglei Miao,Hailong Yang,Maojuan Li...&Jiarong Miao.(2022).KT2 alleviates ulcerative colitis by reducing Th17 cell differentiation through the miR-302c-5p/STAT3 axis.European journal of cell biology,101,(2)
MLA:
Dandan Gu,et al."KT2 alleviates ulcerative colitis by reducing Th17 cell differentiation through the miR-302c-5p/STAT3 axis".European journal of cell biology 101..2(2022):151223