Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles
作者机构:State Key Laboratory of TraumaBurns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China
出 版 物:《Military Medical Research》 (军事医学研究(英文版))
年 卷 期:2024年第11卷第1期
页 面:1-18页
核心收录:
学科分类:100218[医学-急诊医学] 1002[医学-临床医学] 1010[医学-医学技术(可授医学、理学学位)] 10[医学]
基 金:supported by the Key Projects and Innovation Group of National Natural Science Foundation of China(81830065) the Innovation Groups of NSFC(81721001) and the Young Scientists Fund(82102279)
主 题:Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle
摘 要:Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** 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)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P0.05).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(P0.05).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 *** Pericytes are protective a