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 tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease.
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来自肠道微生物群的外膜囊泡介导肾小管间质炎症：糖尿病肾病的潜在新机制。
作者：
Chen PP;Zhang JX;Li XQ;Li L;Wu QY;Liu L;Wang GH;Ruan XZ;Ma KL
Rationale: Chronic tubulointerstitial inflammation is a common pathological process in diabetic kidney disease (DKD). However, its underlying mechanism is largely unknown. This study aims at investigating the role of gut microbiota-derived outer membrane vesicles (OMVs) in tubulointerstitial inflammation in DKD. Methods: Gut microbiota in diabetes mellitus rats was manipulated by microbiota depletion and fecal microbiota transplantation to explore its role in tubulointerstitial inflammation. To check the direct effects of OMVs, fecal bacterial extracellular vesicles (fBEVs) were administrated to mice orally and HK-2 cells in vitro. For mechanistic investigations, HK-2 cells were treated with small interfering RNA against caspase-4 and fBEVs pre-neutralized by polymyxin B. Results: By performing gut microbiota manipulation, it was confirmed that gut microbiota mediated tubulointerstitial inflammation in DKD. In diabetic rats, gut microbiota-derived OMVs were increased and were clearly detected in distant renal tubulointerstitium. Diabetic fBEVs directly administered by gavage translocated into tubular epithelial cells and induced tubulointerstitial inflammation and kidney injury. In vitro, OMVs were internalized through various endocytic pathways and triggered cellular inflammatory response. Mechanistically, it was revealed that OMVs-derived lipopolysaccharide induced tubular inflammation, which was mediated by the activation of the caspase-11 pathway. Conclusions: Increased OMVs due to dysbiosis translocated through leaky gut barrier into distant tubulointerstitium and induced cellular inflammation and renal tubulointerstitial injury in DKD. These findings enrich the mechanism understanding of how gut microbiota and its releasing OMVs influence the development and progression of kidney disease.
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影响因子：
5.2
作者：
Lee J;Yoon YJ;Kim JH;Dinh NTH;Go G;Tae S;Park KS;Park HT;Lee C;Roh TY;Di Vizio D;Gho YS
通讯作者：
Gho YS
影响因子：
6.4
作者：
Finethy R;Luoma S;Orench-Rivera N;Feeley EM;Haldar AK;Yamamoto M;Kanneganti TD;Kuehn MJ;Coers J
通讯作者：
Coers J
影响因子：
3.7
作者：
Ichii O;Otsuka-Kanazawa S;Nakamura T;Ueno M;Kon Y;Chen W;Rosenberg AZ;Kopp JB
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Kopp JB
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影响因子：
19.6
作者：
Miao, Naijun;Yin, Fan;Lu, Limin
通讯作者：
Lu, Limin
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影响因子：
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作者：
Huang, Yun;Li, Si-Cheng;Fang, Chen
通讯作者：
Fang, Chen