Lei Xiao, Zhang Limei, Li Zonglin, Ren Jigang
Traditional Chinese Medicine Department, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, People's Republic of China,
Drug Des Devel Ther. 2018 Sep 6;12:2785-2793. doi: 10.2147/DDDT.S166525. eCollection 2018.
This study aims to figure out the mechanism of astragaloside IV (AS-IV) in the protection of podocyte apoptosis in diabetic nephropathy (DN) rats.
Streptozotocin (STZ) was used to induce diabetes in rats, and the diabetic rats were treated with 5 mg/kg/d of AS-IV for 12 weeks. Albuminuria level, relative TUG1 and TRAF5 levels, and TRAF5 and cleaved-caspase-3 protein levels were examined by ELISA, quantitative reverse transcription (qRT)-PCR, and Western blot analyses, respectively. The interaction between TUG1 and TRAF5 was confirmed by RNA pull-down and RNA precipitation. TUNEL assay was used to detect podocyte apoptosis.
Compared with control rats, DN rats had higher albuminuria and TRAF5 levels and lower TUG1 level. AS-IV treatment attenuated albuminuria and TRAF5 levels and improved TUG1 level in DN rats. TUG1 was downregulated and TRAF5 was upregulated in high-glucose-treated MPC5 cells, and AS-IV ameliorated the TUG1 level. In addition, TUG1 interacted with TRAF5, and TUG1 overexpression promoted degradation of TRAF5 protein. Besides, AS-IV modulated TRAF5 expression through regulating TUG1. AS-IV decreased podocyte apoptosis via the TUG1/TRAF5 pathway. Finally, in vivo experiment proved that si-TUG1 abrogated the protective effect of AS-IV on DN.
AS-IV attenuated podocyte apoptosis and protected diabetic rats from DN via the lncRNA-TUG1/TRAF5 pathway.
本研究旨在探讨黄芪甲苷IV（AS-IV）对糖尿病肾病（DN）大鼠足细胞凋亡的保护机制。
用链脲佐菌素（STZ）诱导大鼠糖尿病，将糖尿病大鼠用5mg/kg/d的AS-IV治疗12周。分别通过酶联免疫吸附测定（ELISA）、定量逆转录（qRT）-PCR和蛋白质免疫印迹分析检测蛋白尿水平、相对TUG1和TRAF5水平以及TRAF5和裂解的半胱天冬酶-3蛋白水平。通过RNA下拉和RNA沉淀证实TUG1与TRAF5之间的相互作用。采用TUNEL法检测足细胞凋亡。
与对照大鼠相比，DN大鼠蛋白尿和TRAF5水平较高，TUG1水平较低。AS-IV治疗可减轻DN大鼠的蛋白尿和TRAF5水平，并提高TUG1水平。在高糖处理的MPC5细胞中TUG1下调，TRAF5上调，AS-IV改善了TUG1水平。此外，TUG1与TRAF5相互作用，TUG1过表达促进TRAF5蛋白降解。此外，AS-IV通过调节TUG1来调节TRAF5表达。AS-IV通过TUG1/TRAF5途径减少足细胞凋亡。最后，体内实验证明si-TUG1消除了AS-IV对DN的保护作用。
AS-IV通过lncRNA-TUG1/TRAF5途径减轻足细胞凋亡，保护糖尿病大鼠免受DN侵害。
