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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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-021-00795-y |
| _version_ | 1818743382820782080 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-18T02:27:32Z |
| format | Article |
| id | doaj.art-dd80fc2ae5d3473484663da382f684c1 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-18T02:27:32Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-dd80fc2ae5d3473484663da382f684c12022-12-21T21:24:00ZengBMCCell Communication and Signaling1478-811X2021-11-0119112010.1186/s12964-021-00795-yThe protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsisHenan Zhou0Danyang Zheng1Hongchen Wang2Yue Wu3Xiaoyong Peng4Qinghui Li5Tao Li6Liangming Liu7State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityState Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical UniversityAbstract 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 Abstracthttps://doi.org/10.1186/s12964-021-00795-yPericyteMicrovesiclesSepsisCTGF |
| spellingShingle | 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 Cell Communication and Signaling Pericyte Microvesicles Sepsis CTGF |
| title | 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_short | 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 |
| topic | Pericyte Microvesicles Sepsis CTGF |
| url | https://doi.org/10.1186/s12964-021-00795-y |
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