The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis

Abstract Background It is well known that sepsis is a prevalent severe disease caused by infection and the treatment strategies are limited. Recently pericyte-derived microvesicles (PMVs) were confirmed to be therapeutic in many diseases, whether PMVs can protect vascular endothelial cell (VEC) inju...

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Autores principales:	Henan Zhou, Danyang Zheng, Hongchen Wang, Yue Wu, Xiaoyong Peng, Qinghui Li, Tao Li, Liangming Liu
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Pericyte Microvesicles Sepsis CTGF Medicine R Cytology QH573-671
Acceso en línea:	https://doaj.org/article/dd80fc2ae5d3473484663da382f684c1
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spelling	oai:doaj.org-article:dd80fc2ae5d3473484663da382f684c12021-11-21T12:13:41ZThe protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis10.1186/s12964-021-00795-y1478-811Xhttps://doaj.org/article/dd80fc2ae5d3473484663da382f684c12021-11-01T00:00:00Zhttps://doi.org/10.1186/s12964-021-00795-yhttps://doaj.org/toc/1478-811XAbstract Background It is well known that sepsis is a prevalent severe disease caused by infection and the treatment strategies are limited. Recently pericyte-derived microvesicles (PMVs) were confirmed to be therapeutic in many diseases, whether PMVs can protect vascular endothelial cell (VEC) injury is unknown. Methods Pericytes were extracted from the retina of newly weaned rats, and PMVs were collected after starvation and characterized by flow-cytometry and transmission electron microscopy. First, the effect of PMVs on pulmonary vascular function in septic rats was measured via intravenous administration with HE staining, immunofluorescence, and Elisa analysis. Then, PMVs were co-incubated with VECs in the presence of lipopolysaccharide (LPS), and observed the protective effect of PMVs on VECs. Next, the proteomic analysis and further Gene Ontology (GO) enrichment analysis were performed to analyze the therapeutic mechanism of PMVs, and the angiogenesis-related protein CTGF was highly expressed in PMVs. Finally, by CTGF upregulation and downregulation in PMV, the role of PMV-carried CTGF was investigated. Results PMVs restored the proliferation and angiogenesis ability of pulmonary VECs, and alleviated pulmonary vascular leakage in septic rats and LPS-stimulated VECs. Further study showed that PMVs delivered CTGF to VECs, and subsequently activated ERK1/2, and increased the phosphorylation of STAT3, thereby improving the function of VECs. The further study found CD44 mediated the absorption and internalization of PMVs to VECs, the anti-CD44 antibody inhibited the protective effect of PMVs. Conclusions PMVs may delivery CTGF to VECs, and promote the proliferation and angiogenesis ability by activating the CTGF-ERK1/2-STAT3 axis, thereby protecting pulmonary vascular function in sepsis. The therapeutic effect of PMVs was highly related to CD44-mediated absorption. Video AbstractHenan ZhouDanyang ZhengHongchen WangYue WuXiaoyong PengQinghui LiTao LiLiangming LiuBMCarticlePericyteMicrovesiclesSepsisCTGFMedicineRCytologyQH573-671ENCell Communication and Signaling, Vol 19, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pericyte Microvesicles Sepsis CTGF Medicine R Cytology QH573-671
spellingShingle	Pericyte Microvesicles Sepsis CTGF Medicine R Cytology QH573-671 Henan Zhou Danyang Zheng Hongchen Wang Yue Wu Xiaoyong Peng Qinghui Li Tao Li Liangming Liu The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis
description	Abstract Background It is well known that sepsis is a prevalent severe disease caused by infection and the treatment strategies are limited. Recently pericyte-derived microvesicles (PMVs) were confirmed to be therapeutic in many diseases, whether PMVs can protect vascular endothelial cell (VEC) injury is unknown. Methods Pericytes were extracted from the retina of newly weaned rats, and PMVs were collected after starvation and characterized by flow-cytometry and transmission electron microscopy. First, the effect of PMVs on pulmonary vascular function in septic rats was measured via intravenous administration with HE staining, immunofluorescence, and Elisa analysis. Then, PMVs were co-incubated with VECs in the presence of lipopolysaccharide (LPS), and observed the protective effect of PMVs on VECs. Next, the proteomic analysis and further Gene Ontology (GO) enrichment analysis were performed to analyze the therapeutic mechanism of PMVs, and the angiogenesis-related protein CTGF was highly expressed in PMVs. Finally, by CTGF upregulation and downregulation in PMV, the role of PMV-carried CTGF was investigated. Results PMVs restored the proliferation and angiogenesis ability of pulmonary VECs, and alleviated pulmonary vascular leakage in septic rats and LPS-stimulated VECs. Further study showed that PMVs delivered CTGF to VECs, and subsequently activated ERK1/2, and increased the phosphorylation of STAT3, thereby improving the function of VECs. The further study found CD44 mediated the absorption and internalization of PMVs to VECs, the anti-CD44 antibody inhibited the protective effect of PMVs. Conclusions PMVs may delivery CTGF to VECs, and promote the proliferation and angiogenesis ability by activating the CTGF-ERK1/2-STAT3 axis, thereby protecting pulmonary vascular function in sepsis. The therapeutic effect of PMVs was highly related to CD44-mediated absorption. Video Abstract
format	article
author	Henan Zhou Danyang Zheng Hongchen Wang Yue Wu Xiaoyong Peng Qinghui Li Tao Li Liangming Liu
author_facet	Henan Zhou Danyang Zheng Hongchen Wang Yue Wu Xiaoyong Peng Qinghui Li Tao Li Liangming Liu
author_sort	Henan Zhou
title	The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis
title_short	The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis
title_full	The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis
title_fullStr	The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis
title_full_unstemmed	The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis
title_sort	protective effects of pericyte-derived microvesicles on vascular endothelial functions via ctgf delivery in sepsis
publisher	BMC
publishDate	2021
url	https://doaj.org/article/dd80fc2ae5d3473484663da382f684c1
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The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis

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