Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles

Zi-Sen Zhang; Yi-Yan Liu; Shuang-Shuang He; Dai-Qin Bao; Hong-Chen Wang; Jie Zhang; Xiao-Yong Peng; Jia-Tao Zang; Yu Zhu; Yue Wu; Qing-Hui Li; Tao Li; Liang-Ming Liu

doi:10.1186/s40779-023-00442-2

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Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles

RESEARCH | Updated：2025-12-13

- Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles
- Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles
- MMR 2024年11卷第1期页码：1-18
- Affiliations：
  
  State Key Laboratory of Trauma, Burns and Combined Injury, Department of Shock and Transfusion, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing 400042, China
- Author bio：
  
  * lt200132@tmmu.edu.cn;
  lmliu62@tmmu.edu.cn
- Funds：
  
  the Key Projects and Innovation Group of National Natural Science Foundation of China(81830065);the Innovation Groups of NSFC(81721001);the Young Scientists Fund(82102279)
- DOI：10.1186/s40779-023-00442-2
  中图分类号：
- 纸质出版：2024-02
- Accepted：
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Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles[J]. MMR, 2024,11(1):1-18.

Cite this article as: Zhang ZS, Liu YY, He SS, Bao DQ, Wang HC, Zhang J, et al. Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles. Mil Med Res. 2023;10(1):13.
Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles[J]. MMR, 2024,11(1):1-18. DOI： 10.1186/s40779-023-00442-2.

Cite this article as: Zhang ZS, Liu YY, He SS, Bao DQ, Wang HC, Zhang J, et al. Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles. Mil Med Res. 2023;10(1):13. DOI： 10.1186/s40779-023-00442-2.

摘要

Abstract

Background

Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis. We hypothesized that pericytes

a group of pluripotent cells that maintain vascular integrity and tension

are protective against sepsis

via

regulating vascular reactivity and permeability.

Methods

We conducted a series of

in vivo

experiments using wild-type (WT)

platelet-derived growth factor receptor-β (PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43

flox/flox

mice to examine the relative contribution of pericytes in sepsis

either induced by cecal ligation and puncture (CLP) or lipopolysaccharide (LPS) challenge. In a separate set of experiments with Sprague–Dawley (SD) rats

pericytes were depleted using CP-673451

a selective PDGFR-β inhibitor

at a dosage of 40 mg/(kg·d) for 7 consecutive days. Cultured pericytes

vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were used for mechanistic investigations. The effects of pericytes and pericyte-derived microvesicles (PCMVs) and candidate miRNAs on vascular reactivity and barrier function were also examined.

Results

CLP and LPS induced severe injury/loss of pericytes

vascular hyporeactivity and leakage (

0.05). Transplantation with exogenous pericytes protected vascular reactivity and barrier function

via

microvessel colonization (

0.05). Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels (

0.05). Additionally

PCMVs transferred miR-145 and miR-132 to VSMCs and VECs

respectively

exerting a protective effect on vascular reactivity and barrier function after sepsis (

0.05). miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2 (Sphk2)/sphingosine-1-phosphate receptor (S1PR) 1/phosphorylation of myosin light chain 20 pathway

whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.

Conclusions

Pericytes are protective against sepsis through regulating vascular reactivity and barrier function. Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.

关键词

Keywords

references

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