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ABSTRACT: Inhibitor of differentiation-2 protein ameliorates DSS-induced ulcerative colitis

PROVIDER: PRJNA756444 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15566500_1.fastq.gz	Fastqsanger.gz
	SRR15566500_2.fastq.gz	Fastqsanger.gz
	SRR15566501_1.fastq.gz	Fastqsanger.gz
	SRR15566501_2.fastq.gz	Fastqsanger.gz
	SRR15566502_1.fastq.gz	Fastqsanger.gz

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Project description:Ulcerative colitis (UC), a form of inﬂammatory bowel disease, is characterized by a Q7 recurrent and persistent nonspeciﬁc inﬂammatory response. Polydatin (PD), a natural stilbenoid polyphenol with potent properties, exhibits unexpected beneﬁcial effects beyond its well-documented anti-inﬂammatory and antioxidant activities. In this study, we presented evidence that PD confers protection against dextran sodium sulfate (DSS)-induced ulcerative colitis. Our ﬁndings demonstrated that PD mitigated the DSS-induced increases in proinﬂammatory cytokines (IL-6, TNF-α, and IL-1β), alleviated colon length shortening, reduced morphological damage to the intestinal mucosa, and preserved tight junction proteins (TJ) occludin and Zonula occludens-1 (ZO-1) in both Caco-2 cells and murine models of colitis. Results from bulk RNA sequencing and differential gene analysis suggested a potential role for ferroptosis in the protective mechanisms of PD against UC. Further investigations revealed that PD modulated the expression levels of several ferroptosis-related proteins and transcription factors within the DSS-induced colitis model. Notably, treatment with PD enhanced nuclear translocation of Nrf2, which inhibits ferroptosis while ameliorating oxidative stress through upregulation of Slc7a11 and Gpx4 expression. Additionally, erastin—a known inducer of ferroptosis—reversed the protective effects conferred by PD in the DSS-induced colitis model by downregulating Slc7a11 expression. These ﬁndings underscore that PD protects against DSS-induced ulcerative colitis via the Nrf2/ Slc7a11/Gpx4 signaling axis, highlighting its potential as a novel therapeutic agent for UC.

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