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Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury

Peritubular capillaries (PTCs) are closely related to renal tubules in structure and function, and both are pivotal regulators in the development and progression of acute kidney injury (AKI). However, the mechanisms that underlie the interaction between PTCs and tubules during AKI remain unclear. He...

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Autores principales: Zhong, Xin, Tang, Tao-Tao, Shen, An-Ran, Cao, Jing-Yuan, Jing, Jing, Wang, Cui, Zhu, Xiao-Xiao, Wen, Yi, Li, Zuo-Lin, Wang, Bin, Qin, Suo-Fu, Liu, Bi-Cheng, Lv, Lin-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759551/
https://www.ncbi.nlm.nih.gov/pubmed/36528739
http://dx.doi.org/10.1038/s41536-022-00268-x
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author Zhong, Xin
Tang, Tao-Tao
Shen, An-Ran
Cao, Jing-Yuan
Jing, Jing
Wang, Cui
Zhu, Xiao-Xiao
Wen, Yi
Li, Zuo-Lin
Wang, Bin
Qin, Suo-Fu
Liu, Bi-Cheng
Lv, Lin-Li
author_facet Zhong, Xin
Tang, Tao-Tao
Shen, An-Ran
Cao, Jing-Yuan
Jing, Jing
Wang, Cui
Zhu, Xiao-Xiao
Wen, Yi
Li, Zuo-Lin
Wang, Bin
Qin, Suo-Fu
Liu, Bi-Cheng
Lv, Lin-Li
author_sort Zhong, Xin
collection PubMed
description Peritubular capillaries (PTCs) are closely related to renal tubules in structure and function, and both are pivotal regulators in the development and progression of acute kidney injury (AKI). However, the mechanisms that underlie the interaction between PTCs and tubules during AKI remain unclear. Here we explored a new mode of tubulovascular crosstalk mediated by small extracellular vesicles (sEV) after AKI. In response to renal ischemia/reperfusion (I/R) injury, endothelial proliferation of PTCs and tubular expression of vascular endothelial growth factor-A (VEGF-A) were increased, accompanied by a remarkable redistribution of cytoplasmic VEGF-A to the basolateral side of tubular cells. Meanwhile, the secretion mode of VEGF-A was converted in the injured tubular cells, which showed a much greater tendency to secrete VEGF-A via sEV other than the free form. Interestingly, tubular cell-derived VEGF-A-enriched sEV (sEV-VEGF-A) turned out to promote endothelial proliferation which was regulated by VEGF receptors 1 and 2. Furthermore, inhibition of renal sEV secretion by Rab27a knockdown resulted in a significant decrease in the proliferation of peritubular endothelial cells in vivo. Importantly, taking advantage of the newly recognized endogenous repair response of PTCs, exogenous supplementation of VEGF-A + sEV efficiently recused PTC rarefaction, improved renal perfusion, and halted the AKI to CKD transition. Taken together, our study uncovered a novel intrinsic repair response after AKI through renal tubule-PTC crosstalk via sEV-VEGF-A, which could be exploited as a promising therapeutic angiogenesis strategy in diseases with ischemia.
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spelling pubmed-97595512022-12-19 Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury Zhong, Xin Tang, Tao-Tao Shen, An-Ran Cao, Jing-Yuan Jing, Jing Wang, Cui Zhu, Xiao-Xiao Wen, Yi Li, Zuo-Lin Wang, Bin Qin, Suo-Fu Liu, Bi-Cheng Lv, Lin-Li NPJ Regen Med Article Peritubular capillaries (PTCs) are closely related to renal tubules in structure and function, and both are pivotal regulators in the development and progression of acute kidney injury (AKI). However, the mechanisms that underlie the interaction between PTCs and tubules during AKI remain unclear. Here we explored a new mode of tubulovascular crosstalk mediated by small extracellular vesicles (sEV) after AKI. In response to renal ischemia/reperfusion (I/R) injury, endothelial proliferation of PTCs and tubular expression of vascular endothelial growth factor-A (VEGF-A) were increased, accompanied by a remarkable redistribution of cytoplasmic VEGF-A to the basolateral side of tubular cells. Meanwhile, the secretion mode of VEGF-A was converted in the injured tubular cells, which showed a much greater tendency to secrete VEGF-A via sEV other than the free form. Interestingly, tubular cell-derived VEGF-A-enriched sEV (sEV-VEGF-A) turned out to promote endothelial proliferation which was regulated by VEGF receptors 1 and 2. Furthermore, inhibition of renal sEV secretion by Rab27a knockdown resulted in a significant decrease in the proliferation of peritubular endothelial cells in vivo. Importantly, taking advantage of the newly recognized endogenous repair response of PTCs, exogenous supplementation of VEGF-A + sEV efficiently recused PTC rarefaction, improved renal perfusion, and halted the AKI to CKD transition. Taken together, our study uncovered a novel intrinsic repair response after AKI through renal tubule-PTC crosstalk via sEV-VEGF-A, which could be exploited as a promising therapeutic angiogenesis strategy in diseases with ischemia. Nature Publishing Group UK 2022-12-17 /pmc/articles/PMC9759551/ /pubmed/36528739 http://dx.doi.org/10.1038/s41536-022-00268-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhong, Xin
Tang, Tao-Tao
Shen, An-Ran
Cao, Jing-Yuan
Jing, Jing
Wang, Cui
Zhu, Xiao-Xiao
Wen, Yi
Li, Zuo-Lin
Wang, Bin
Qin, Suo-Fu
Liu, Bi-Cheng
Lv, Lin-Li
Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury
title Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury
title_full Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury
title_fullStr Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury
title_full_unstemmed Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury
title_short Tubular epithelial cells-derived small extracellular vesicle-VEGF-A promotes peritubular capillary repair in ischemic kidney injury
title_sort tubular epithelial cells-derived small extracellular vesicle-vegf-a promotes peritubular capillary repair in ischemic kidney injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759551/
https://www.ncbi.nlm.nih.gov/pubmed/36528739
http://dx.doi.org/10.1038/s41536-022-00268-x
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