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Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation:a potential new mechanism for diabetic kidney disease

Outer membrane vesicles derived from gut microbiota mediate ...

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浙江省免疫学会第十三次学术大会

作者： Peipei Chen Kunling Ma Department of Nephrology the Second Affiliated HospitalSchool of MedicineZhejiang University

Background:Chronic tubulointerstitial inflammation is a common pathological process in diabetic kidney disease(DKD).However,its underlying mechanism is largely ***:This study aims to investigate the role of gut microbiota-derived outer membrane vesicles(OMVs) in tubulointerstitial inflammation in *** and methods:Gut microbiota in diabetes mellitus(DM) rats was manipulated by microbiota depletion and fecal microbiota transplantation(FMT) to explore its role in tubulointerstitial *** check the direct effects of OMVs,fecal bacterial extracellular vesicles(fBEVs) were administrated to mice orally and HK-2 cells in *** mechanistic investigations,HK-2 cells were treated with small interfering RNA against caspase 4 and fBEVs pre-neutralized by polymyxin B(PMB).Results:The increased levels of serum cytokines,upregulated expression levels of inflammatory proteins in the renal cortex and tubular pathological injuries were observed in DM rats,which were alleviated by gut microbiota depletion and FMT treatment,indicating that gut microbiota was involved in systemic and tubulointerstitial inflammation in *** diabetic rats,gut microbiota-derived OMVs were increased and were clearly detected in distant renal tubulointerstitium,which were reduced by gut microbiota depletion and FMT *** was suggested that increased gut microbiota-derived OMVs might be involved in the pathogenesis and progression of *** expression levels of occludin and zona occludens 1 in the colon of DM rats decreased,accompanied by much more OMVs infiltration in *** microbiota depletion and FMT treatment could reverse these *** addition,orally treated DiD-fBEVs could be detected in distant tubulointerstitium of intestine-damaged *** was indicated that gut microbiota-derived OMVs could translocate through disrupted gut barrier into the ***-fBEVs directly administered by gavage translocated into tubular epithel

关键词： diabetic kidney disease renal tubulointerstitial inflammation gut microbiota outer membrane vesicles caspase 11 pathway

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