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Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease

Exosomes are increasingly recognized as vehicles of intercellular communication. However, the role of exosome in maintaining cellular homeostasis under stress conditions remained unclear. Here we show that Rab27a expression was upregulated exclusively in tubular epithelial cells (TECs) during protei...

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Autores principales: Feng, Ye, Zhong, Xin, Tang, Tao-Tao, Wang, Cui, Wang, Li-Ting, Li, Zuo-Lin, Ni, Hai-Feng, Wang, Bin, Wu, Min, Liu, Dan, Liu, Hong, Tang, Ri-Ning, Liu, Bi-Cheng, Lv, Lin-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343869/
https://www.ncbi.nlm.nih.gov/pubmed/32641688
http://dx.doi.org/10.1038/s41419-020-2709-4
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author Feng, Ye
Zhong, Xin
Tang, Tao-Tao
Wang, Cui
Wang, Li-Ting
Li, Zuo-Lin
Ni, Hai-Feng
Wang, Bin
Wu, Min
Liu, Dan
Liu, Hong
Tang, Ri-Ning
Liu, Bi-Cheng
Lv, Lin-Li
author_facet Feng, Ye
Zhong, Xin
Tang, Tao-Tao
Wang, Cui
Wang, Li-Ting
Li, Zuo-Lin
Ni, Hai-Feng
Wang, Bin
Wu, Min
Liu, Dan
Liu, Hong
Tang, Ri-Ning
Liu, Bi-Cheng
Lv, Lin-Li
author_sort Feng, Ye
collection PubMed
description Exosomes are increasingly recognized as vehicles of intercellular communication. However, the role of exosome in maintaining cellular homeostasis under stress conditions remained unclear. Here we show that Rab27a expression was upregulated exclusively in tubular epithelial cells (TECs) during proteinuria nephropathy established by adriamycin (ADR) injection and 5/6 nephrectomy as well as in chronic kidney disease patients, leading to the increased secretion of exosomes carrying albumin. The active exosome production promoted tubule injury and inflammation in neighboring and the producing cells. Interferon regulatory factor 1 (IRF-1) was found as the transcription factor contributed to the upregulation of Rab27a. Albumin could be detected in exosome fraction and co-localized with exosome marker CD63 indicating the secretion of albumin into extracellular space by exosomes. Interestingly, inhibition of exosome release accelerated albumin degradation which reversed tubule injury with albumin overload, while lysosome suppression augmented exosome secretion and tubule inflammation. Our findings revealed that IRF-1/Rab27a mediated exosome secretion constituted a coordinated approach to lysosome degradation for albumin handling, which lead to the augment of albumin toxicity as a maladaptive response to maintain cell homeostasis. The findings may suggest a novel therapeutic strategy for proteinuric kidney disease by targeting exosome secretion.
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spelling pubmed-73438692020-07-13 Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease Feng, Ye Zhong, Xin Tang, Tao-Tao Wang, Cui Wang, Li-Ting Li, Zuo-Lin Ni, Hai-Feng Wang, Bin Wu, Min Liu, Dan Liu, Hong Tang, Ri-Ning Liu, Bi-Cheng Lv, Lin-Li Cell Death Dis Article Exosomes are increasingly recognized as vehicles of intercellular communication. However, the role of exosome in maintaining cellular homeostasis under stress conditions remained unclear. Here we show that Rab27a expression was upregulated exclusively in tubular epithelial cells (TECs) during proteinuria nephropathy established by adriamycin (ADR) injection and 5/6 nephrectomy as well as in chronic kidney disease patients, leading to the increased secretion of exosomes carrying albumin. The active exosome production promoted tubule injury and inflammation in neighboring and the producing cells. Interferon regulatory factor 1 (IRF-1) was found as the transcription factor contributed to the upregulation of Rab27a. Albumin could be detected in exosome fraction and co-localized with exosome marker CD63 indicating the secretion of albumin into extracellular space by exosomes. Interestingly, inhibition of exosome release accelerated albumin degradation which reversed tubule injury with albumin overload, while lysosome suppression augmented exosome secretion and tubule inflammation. Our findings revealed that IRF-1/Rab27a mediated exosome secretion constituted a coordinated approach to lysosome degradation for albumin handling, which lead to the augment of albumin toxicity as a maladaptive response to maintain cell homeostasis. The findings may suggest a novel therapeutic strategy for proteinuric kidney disease by targeting exosome secretion. Nature Publishing Group UK 2020-07-08 /pmc/articles/PMC7343869/ /pubmed/32641688 http://dx.doi.org/10.1038/s41419-020-2709-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Feng, Ye
Zhong, Xin
Tang, Tao-Tao
Wang, Cui
Wang, Li-Ting
Li, Zuo-Lin
Ni, Hai-Feng
Wang, Bin
Wu, Min
Liu, Dan
Liu, Hong
Tang, Ri-Ning
Liu, Bi-Cheng
Lv, Lin-Li
Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
title Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
title_full Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
title_fullStr Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
title_full_unstemmed Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
title_short Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
title_sort rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343869/
https://www.ncbi.nlm.nih.gov/pubmed/32641688
http://dx.doi.org/10.1038/s41419-020-2709-4
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