ISSN: 1838-7640Theranostics
Global reach, higher impact
Theranostics 2023; 13(12):3988-4003. doi:10.7150/thno.84650 This issue Cite
Research Paper
Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease
1. Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
2. People's Hospital Affiliated to Shandong First Medical University, Shandong, 271100, China.
3. John Moorhead Research Laboratory, Department of Renal Medicine, University College London (UCL) Medical School, Royal Free Campus, London, NW3 2PF, UK.
4. Department of Nephrology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China.
Citation:
Chen PP, Zhang JX, Li XQ, Li L, Wu QY, Liu L, Wang GH, Ruan XZ, Ma KL. Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease. Theranostics 2023; 13(12):3988-4003. doi:10.7150/thno.84650. https://www.thno.org/v13p3988.htm
Other stylesAbstract
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.
Keywords: diabetic kidney disease, renal tubulointerstitial inflammation, gut microbiota, outer membrane vesicles, caspase-11 pathway
Citation styles
APA
Chen, P.P., Zhang, J.X., Li, X.Q., Li, L., Wu, Q.Y., Liu, L., Wang, G.H., Ruan, X.Z., Ma, K.L. (2023). Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease. Theranostics, 13(12), 3988-4003. https://doi.org/10.7150/thno.84650.
ACS
Chen, P.P.; Zhang, J.X.; Li, X.Q.; Li, L.; Wu, Q.Y.; Liu, L.; Wang, G.H.; Ruan, X.Z.; Ma, K.L. Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease. Theranostics 2023, 13 (12), 3988-4003. DOI: 10.7150/thno.84650.
NLM
Chen PP, Zhang JX, Li XQ, Li L, Wu QY, Liu L, Wang GH, Ruan XZ, Ma KL. Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease. Theranostics 2023; 13(12):3988-4003. doi:10.7150/thno.84650. https://www.thno.org/v13p3988.htm
CSE
Chen PP, Zhang JX, Li XQ, Li L, Wu QY, Liu L, Wang GH, Ruan XZ, Ma KL. 2023. Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease. Theranostics. 13(12):3988-4003.
This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.