RegIIIγ介导脂肪干细胞对金黄色葡萄菌所致急性肺损伤的保护作用及相关调控机制

Mesenchymal stem cells have shown protective effects on the acute lung injury (ALI)induced by bacteria, but their underlying mechanisms are still unclear.Using a mouse model of S.aurues-induced ALI, our research will illustrate a new protective mechanism for adipose-derived mesenchymal stem cells (ADSCs) in ALI: regenerating islet-derived protein IIIγ（RegIIIγ）mediates the paracrine effects of ADSCs.Furthermore,the effects of overexpression of RegIIIγin the lung by ADSCs or injecting exogenous recombinant RegIIIγ protein on S. aureus-induced ALI and its immune regulatory mechanisms will be explored. In addition,the molecular regulatory mechanism of RegIIIγ in ADSCs infected with S. aureus will be also investigated. Our study provides a novel strategy for the prevention and treatment of S. aureus-induced ALI, and opens up a new way for regenerative medical research.

间充质干细胞对细菌性急性肺损伤（ALI）有良好的保护作用，但其作用机制仍有待阐明。本项目将利用金葡菌诱导的小鼠ALI模型，阐明脂肪来源间充质干细胞（又称脂肪干细胞，ADSCs）对ALI保护作用的一种新机制：再生源蛋白IIIγ（RegIIIγ）介导了ADSCs的旁分泌作用。进一步研究ADSCs作为载体在肺内高表达RegIIIγ或外源导入RegIIIγ重组蛋白对金葡菌ALI的影响和免疫调控机制。同时通过ADSCs体金葡菌外感染模型，探索RegIIIγ的分子调控机制。本研究将为金葡菌感染性ALI的防治提供了新策略，为再生医学研究开辟新的思路。

治疗重症肺炎所致急性肺损伤（ALI）缺乏有效方法。脂肪干细胞（ADSC）是一种具有抗菌和抗炎作用的成体干细胞。本课题研究了ADSC对金黄色葡萄球菌诱导的小鼠ALI的治疗作用。结果表明，气管内滴注ADSC可减轻金葡菌ALI小鼠肺部炎症的严重程度，降低感染小鼠的细菌载量和死亡率。研究还揭示了再生源IIIγ (RegIIIγ)的分泌与脂肪干细胞的保护效应有关，并且RegIIIγ表达受到TLR2-MyD88-JAK2/STAT3信号通路调控。本研究为金葡菌感染性ALI的防治提供了新策略，为再生医学研究开辟新思路。