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Abstract
Abstract Background Individual information transmission is coordinated across tissues by exosomes, and the colonic inflammation response depends on continuous communication with the peripheral blood. Recent report showed exosome derived miRNA could assist in the early diagnosis and monitoring recurrence of ulcerative colitis (UC). However, the role of exosome proteins in colitis remains unknown. Methods We analyzed the clinical information of UC patients in the Department of Gastroenterology of Peking University Third Hospital from January 2022 to October 2023. Then, we assessed plasma exosome mass spectroscope-based proteomics of active UC patients (UCa), UC patients in clinical remission (UCi) and healthy controls (HCs). Finally, we validated the differential proteins expression by western blot in the DSS-induced acute and chronic colitis. Results We retrospectively analyzed the clinical information of 568 UC patients (774 person-time). UC patients whose Mayo endoscopic score was higher had more severe circulating inflammation, and peripheral lower cholesterol, HDL-c and LDL-c were related to a significantly higher degree of colonic inflammation. Using plasma exosome mass spectroscope-based proteomics, we demonstrated that proteome landscape of the plasma exosome was significantly differ among health controls and distinct UC stages, which enriched proteins in UCa group mainly focused on cholesterol metabolism. We further identified a star molecule on the cholesterol metabolism pathway, APOA1, since it was up-regulated both in DSS-induced acute and chronic mice colon, and it might play a significant role in the lipid disturbance of UC. Conclusion We firstly demonstrated that proteome landscape of the plasma exosome among health controls and different UC stages, prompting that cholesterol metabolism might play a significant role in the pathogenesis of UC. In addition, we provided evidence into further investigating of APOA1’s role in the cholesterol metabolism in the context of UC.
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