2. Academic Validation
  3. The protective effects of pericyte-derived microvesicles on vascular endothelial functions via CTGF delivery in sepsis

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

  • Cell Commun Signal. 2021 Nov 16;19(1):115. doi: 10.1186/s12964-021-00795-y.
Henan Zhou 1,  Danyang Zheng 1 2,  Hongchen Wang 1,  Yue Wu 1,  Xiaoyong Peng 1,  Qinghui Li 1,  Tao Li  # 3,  Liangming Liu  # 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical University, No.10th Daping Changjiang Road, Chongqing, 400038, China.
  • 2 Intensive Care Unit, General Hospital of Central Theater Command, Wuhan, 430064, China.
  • 3 State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical University, No.10th Daping Changjiang Road, Chongqing, 400038, China. [email protected].
  • 4 State Key Laboratory of Trauma, Burns and Combined Injury, Shock and Transfusion Department, Army Medical Center of PLA, Daping Hospital, Army Medical University, No.10th Daping Changjiang Road, Chongqing, 400038, China. [email protected].
  • # Contributed equally.
PMID: 34784912 DOI: 10.1186/s12964-021-00795-y
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.

Keywords

CTGF; Microvesicles; Pericyte; Sepsis.

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