SIRT6在呼吸系统疾病中的作用研究进展

Research progress of SIRT6 in respiratory diseases

Sirtuins是一类具有单ADP-核糖基转移酶或脱酰酶活性的蛋白质,涉及影响广泛的细胞过程,如衰老、转录、细胞凋亡、炎症和抗压力,以及低热量情况下的能量效率和警觉性。Sirtuins还可以控制生物钟和线粒体生物发生。哺乳动物有7个Sirtuins。SIRT6属于Sir2蛋白家族中的一员,目前已知其拥有NAD+依赖的组蛋白去乙酰化酶、单ADP核糖基转移酶及去脂肪酰化酶等多种催化功能。SIRT6通过这数种催化功能参与机体多种生命过程,在调控DNA修复、端粒维护、炎症反应、能量代谢以及癌症的发生与发展等方面发挥重要作用。本文对SIRT6在慢性阻塞性肺疾病、特发性肺纤维化、哮喘、非小细胞肺癌等呼吸系统疾病中的作用进行综述。在慢阻肺的发病机制上,SIRT6起肺衰老的作用,表现在DNA损伤、端粒缩短、细胞自噬等相似之处。SIRT6在特发性肺纤维化中参与了肺上皮间质转化,抵抗博莱霉素诱导的肺内EMT,表现出抵抗纤维化的作用。SIRT6的去乙酰化作用可以介导支气管哮喘的气道炎症减轻,也参与自身免疫性炎症的过程。SIRT6在非小细胞肺癌的形成及生长维持中起关键作用。了解SIRT6在呼吸系统里的作用有利于揭示疾病机制及开拓全新的治疗靶位或研制新药物。

Sirtuins are a class of proteins that possess either mono-ADP-ribosyltransferase, or deacylase activity. Sirtuins have been implicated in influencing a wide range of cellular processes like aging, transcription, apoptosis, inflammation and stress resistance, as well as energy efficiency and alertness during low-calorie situations. Sirtuins can also control circadian clocks and mitochondrial biogenesis. Mammals possess seven sirtuins(SIRT1-7). SIRT6, a member of the Sir2 protein family, is known to have NAD+ dependent histone deacetylase, mono-ADP-ribotransferase and deadipoacylase catalysis. Through these functions, SIRT6 plays an important role in regulating DNA repair, telomere maintenance, inflammatory response and the occurrence and development of cancer. This paper reviews the role of SIRT6 in chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, non-small cell lung cancer, and other respiratory diseases. In terms of the pathogenesis of COPD, SIRT6 plays a role in lung aging, which is manifested in DNA damage, telomere shortening, and, autophagy. SIRT6 is involved in pulmonary epithelial-mesenchymal transition(EMT) in idiopathic pulmonary fibrosis, and it is resistant to intrapulmonary EMT induced by bleomycin, showing that the role of resistance to fibrosis. SIRT6 deacetylation can mediate the reduction of airway inflammation in bronchial asthma and also participate in the process of autoimmune inflammation. SIRT6 plays a key role in the formation and growth maintenance of NSCLC. Understanding the role of SIRT6 in the respiratory system is conducive to revealing the disease mechanism and exploring new therapeutic targets or developing new drugs.