HBO1促进TGF-β1介导的自噬影响人胎盘MSCs治疗肺纤维化的作用机制研究

肺纤维化（PF）是由肺损伤及过度炎症引起的间质性肺病，发病机制复杂，缺乏有效疗法，死亡率逐年增加。研究表明，PF相关病理微环境介导的自噬与间充质干细胞（MSCs）生物功能密切相关，干预自噬可提升MSCs的治疗潜能。我们前期发现：HBO1促进TGF-β1介导的人胎盘胎儿来源MSCs（fPMSCs）自噬，诱发细胞衰老，干扰HBO1可提高fPMSCs治疗PF的作用。由此，我们推测HBO1表观修饰调控PF病理微环境诱导的自噬，影响fPMSCs对PF的疗效。项目拟完成：①确定HBO1与PF病理微环境诱导fPMSCs自噬及衰老的调控关系；②研究HBO1调控TGF-β1介导自噬促进fPMSCs衰老的分子机制；③明晰干预HBO1对fPMSCs治疗PF的影响及机理。本项目的实施将明晰HBO1对PF病理微环境诱导fPMSCs自噬及衰老的调控作用及分子机制，为MSCs治疗PF新策略的提出提供理论基础和实验依据。

Pulmonary fibrosis (PF) is a pulmonary interstitial disease caused by lung injury and inflammatory response. Pathogenesis is complicated. Clinically, there is still a lack of effective treatment to PF, and its mortality rate remains high. Some studies have demonstrated that autophagy induced by PF pathological microenvironment can affect biological functions of MSCs, while the therapeutic potential of MSCs can be elevated by regulating autophagy. Our recent work discovered that autophagy and senescenece of human placental mesenchymal stem cells of fetal origin (fPMSCs) induced by TGF-β1 can be promoted by HBO1, decreasing the expression of HBO1 has the capability to enhance therapeutic effects of fPMSCs to PF. Thus we hypothesize that HBO1 regulates epigenetically autophagy of placental mesenchymal stem cells induced by pulmonary fibrosis pathological microenvironment, and influence the therapeutic effects of fPMSCs in PF. Based on these results, the present project is designed to accomplish the following works: 1. to ascertain the regulatory relationship between HBO1 and autophagy/senescence of fPMSCs induced by PF pathological microenvironment; 2.to analyze the molecular mechanism of HBO1 regulates autophagy mediated by TGF-β1 to promote senescence of fPMSCs; 3. to clarify inhibition of HBO1 influences the therapeutic effects of fPMSCs on PF and its potential principle. The results of these studies will partialy illustrate the functions and mechanism of HBO1 regulates autophagy of fPMSCs in a PF pathological microenvironment. This will provide the theoretical basis and experimental evidence for new strategies to optimize MSCs treatment for PF.