The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis.
Henan Zhou,Danyang Zheng,Hongchen Wang,Yue Wu,Xiaoyong Peng,Qing-Hui Li,Tao Li,Liangming Liu +7 more
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TLDR
In this paper, pericyte-derived microvesicles (PMVs) were confirmed to be therapeutic in many diseases, whether PMVs can protect vascular endothelial cell (VEC) injury is unknown.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.read more
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The Emerging Role of Pericyte-Derived Extracellular Vesicles in Vascular and Neurological Health
Kushal Sharma,Yunpei Zhang,Keshav Raj Paudel,Allan Kachelmeier,Philip M. Hansbro,Xiaorui Shi +5 more
TL;DR: Current research on the characteristic features of EVs secreted by PCs and their role in neuronal and vascular health and disease are discussed.
Journal ArticleDOI
Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles
Zisen Zhang,Yi-Yan Liu,Shuang-Shuang He,Daiqin Bao,Hongchen Wang,Jie Jun Zhang,Xiaoyong Peng,Jiatao Zang,Yu Zhu,Yue Wu,Qing-Hui Li,Tao Li,Liangming Liu +12 more
TL;DR: In this article , pericytes, a group of pluripotent cells that maintain vascular integrity and tension, are hypothesized to be protective against sepsis via regulating vascular reactivity and permeability.
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