SIRT7 regulates the TGF-beta 1-induced proliferation and migration of mouse airway smooth muscle cells by modulating the expression of TGF-beta receptor I

摘要

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-beta 1). Knockdown of SIRT7 inhibited the proliferation, promoted the apoptosis, and suppressed the migration of TGF-beta 1-treated ASM cells, while overexpression of SIRT7 had the opposite effect. Moreover, knockdown of SIRT7 inhibited protein expression of the TGF-beta receptor I (T beta RI), whilst overexpression of SIRT7 promoted the expression of T beta RI. Importantly, knockdown of T beta RI partially reversed the stimulatory effect of SIRT7 overexpression on the TGF-beta 1-induced proliferation and migration of ASM cells. Taken together, these results demonstrate that SIRT7 is involved in regulating TGF-beta 1-induced ASM cell proliferation and migration by regulating the expression of T beta RI, thus indicating an important role of SIRT7 during airway remodeling in asthma.