茶多酚调节STAT3/miR-126/端粒信号通路活性延缓高糖诱导的人肾小球系膜细胞衰老

探讨茶多酚(tea polyphenols,TP)在体外高糖环境下延缓人肾小球系膜细胞(human glomerular mesangial cells,HGMCs)衰老的作用及可能的机制。在体外培养HGMCs,分为正常组(normal group,N,5.5 mmol·L^-1葡萄糖)、甘露醇组(mannitol group,MNT,5.5 mmol·L^-1葡萄糖+24.5 mmol·L^-1甘露醇)、高糖组(high dose of D-glucose group,HG,30 mmol·L^-1葡萄糖)、低剂量TP组(low dose of TP group,L-TP,30 mmol·L^-1葡萄糖+5 mg·L^-1 TP)及高剂量TP组(high dose of TP group,H-TP,30 mmol·L^-1葡萄糖+20 mg·L^-1 TP),分别在37℃,5%CO2条件下培养,干预72 h后,首先观察TP对HGMCs形态的影响;其次,检测细胞周期、衰老相关半乳糖苷酶(senescence-associated-β-galactosidase,SA-β-gal)染色阳性率、端粒长度;最后,检测p53-p21-Rb信号通路中关键信号分子p53,p21,Rb的蛋白表达水平及p-STAT3,miR-126的表达水平。结果表明,高糖能诱导HGMCs衰老,不仅表现为细胞周期阻滞于G1期、SA-β-gal染色阳性率升高、端粒长度缩短,还表现为p53,p21,Rb蛋白表达水平升高和p53-p21-Rb信号通路激活。L-TP能延缓HGMCs衰老,不仅表现为HGMCs细胞周期G1期阻滞的改善、SA-β-gal染色阳性率的下降、端粒长度的延长,还表现为p53,p21,Rb蛋白表达水平的下降,端粒-p53-p21-Rb信号通路活性的抑制。此外,高糖诱导HGMCs p-STAT3表达水平上调、miR-126表达水平下调,而L-TP可使这些变化得到改善。总之,高糖能激活端粒-p53-p21-Rb信号通路而诱导HGMCs衰老;L-TP能调节STAT3/miR-126表达水平,抑制端粒-p53-p21-Rb信号通路活性而延缓高糖诱导的HGMCs衰老。这些发现为临床上防治糖尿病肾病相关的肾脏细胞衰老提供了有效的干预措施。

Tea polyphenols delays human glomerular mesangial cells senescence induced by high glucose via regulating STAT3/miR-126/telomere signaling pathway activation

CAO Dong-wei;HAN Wen-bei;HE Jin-song;ZHAO Min;JIANG Chun-ming;ZHANG Qing-yan;WAN Cheng;LIU Jing;FENG Yuan;JIN Bo;YANG Bo;ZHU Da-long;HAN Xiao(Department of Nephrology,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University,Nanjing 210008,China;Department of Nephrology,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanfing 210008,China;Department of Traditional Chinese Medicine,Nanjing Drum Tower Hospital Clinical College of Chinese Medicine and Western Medicine,Nanfing University of Chinese Medicine,Nanfing 210008,China;Department of Dermatology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Department of Endocrinology,Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University,Nanjing 210008,China;Nanjing Medical University,Basic Medical School,Nanjing 210000,China)