Division of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, School of Medicine, Xi'an, 710004, Shaanxi, PR China.
Division of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, School of Medicine, Xi'an, 710004, Shaanxi, PR China; Internal Medicine Department, Section Four, Xi'an Chest Hospital, Xi'an, 710100, Shaanxi, PR China.
Biomed Pharmacother. 2018 Aug;104:781-787. doi: 10.1016/j.biopha.2018.05.060. Epub 2018 May 29.
Accumulating evidence shows that sirtuin 7 (SIRT7), a key mediator of many cellular activities, plays an important role in the pathogenesis of various diseases; however, little is known about the role of SIRT7 in asthma, which is characterized by airway remodeling. This study investigated the potential role of SIRT7 in regulating the proliferation and migration of airway smooth muscle (ASM) cells, which are critical events during airway remodeling in asthmatic conditions. The results demonstrated that SIRT7 expression was significantly upregulated in ASM cells treated with transforming growth factor-beta 1 (TGF-β1). Knockdown of SIRT7 inhibited the proliferation, promoted the apoptosis, and suppressed the migration of TGF-β1-treated ASM cells, while overexpression of SIRT7 had the opposite effect. Moreover, knockdown of SIRT7 inhibited protein expression of the TGF-β receptor I (TβRI), whilst overexpression of SIRT7 promoted the expression of TβRI. Importantly, knockdown of TβRI partially reversed the stimulatory effect of SIRT7 overexpression on the TGF-β1-induced proliferation and migration of ASM cells. Taken together, these results demonstrate that SIRT7 is involved in regulating TGF-β1-induced ASM cell proliferation and migration by regulating the expression of TβRI, thus indicating an important role of SIRT7 during airway remodeling in asthma.
越来越多的证据表明,作为许多细胞活动的关键介质,Sirtuin 7(SIRT7)在各种疾病的发病机制中起着重要作用;然而,人们对 SIRT7 在哮喘中的作用知之甚少,哮喘的特征是气道重塑。本研究探讨了 SIRT7 在调节气道平滑肌(ASM)细胞增殖和迁移中的潜在作用,这是哮喘情况下气道重塑过程中的关键事件。结果表明,转化生长因子-β1(TGF-β1)处理后的 ASM 细胞中 SIRT7 表达明显上调。SIRT7 敲低抑制 TGF-β1 处理的 ASM 细胞的增殖,促进细胞凋亡,并抑制细胞迁移,而过表达 SIRT7 则产生相反的效果。此外,SIRT7 敲低抑制 TGF-β 受体 I(TβRI)的蛋白表达,而过表达 SIRT7 则促进 TβRI 的表达。重要的是,TβRI 的敲低部分逆转了 SIRT7 过表达对 TGF-β1 诱导的 ASM 细胞增殖和迁移的刺激作用。综上所述,这些结果表明,SIRT7 通过调节 TβRI 的表达参与调节 TGF-β1 诱导的 ASM 细胞增殖和迁移,这表明 SIRT7 在哮喘中的气道重塑过程中起着重要作用。