Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, P.O. box 11381, Abbassia, Cairo, Egypt.
Pharmacology Department, Faculty of Medicine, Ain Shams University, P.O. box 11381, Abbassia, Cairo, Egypt.
Sci Rep. 2017 May 23;7(1):2263. doi: 10.1038/s41598-017-02320-z.
The aim of this study is to evaluate the anti-diabetic nephropathy effect of Caffeic acid and to prove our hypothesis for its mechanism of action that it may occur by reactivation of autophagy pathway via suppression of autophagy regulatory miRNAs. In vivo, high-fat diet and streptozotocin-induced (HFD-STZ) diabetic rats were treated with Caffeic acid once per day for 12 weeks before and after development of diabetic nephropathy. Blood and urine biochemical parameters, autophagy transcripts and their epigenetic regulators together with renal tissue morphology were investigated. In diabetic rats, Caffeic acid intake, caused improvement in albumin excretion,blood glucose, reduced renal mesangial matrix extension with increased vacuolation and reappearance of autophagosomes. Meanwhile, it resulted in autophagy genes up-regulation [RB 1-inducible coiled coil protein (RB1CC1), Microtubule-associated proteins 1A/1B light chain 3(MAP1LC3B), Autophagy related gene (ATG-12),] with simultaneous reduction in their epigenetic regulators; miRNA-133b, -342 and 30a, respectively. These above mentioned effects were more significant in the diabetic nephropathy Caffeic treated rats than in the prophylactic group. Based on our results we postulated that caffeic acid modulates autophagy pathway through inhibition of autophagy regulatory miRNAs, that could explain its curative properties against diabetic kidney disease.
本研究旨在评估咖啡酸对糖尿病肾病的防治作用，并验证其作用机制假说，即通过抑制自噬调控 miRNA 来激活自噬途径。在体内，高糖高脂饮食联合链脲佐菌素（HFD-STZ）诱导的糖尿病大鼠在糖尿病肾病发生前和发生后每天给予咖啡酸一次，共 12 周。检测血液和尿液生化参数、自噬转录物及其表观遗传调控因子以及肾脏组织形态。在糖尿病大鼠中，咖啡酸摄入可改善白蛋白排泄、血糖，减少肾小球系膜基质扩张，增加空泡形成，恢复自噬体。同时，它还导致自噬基因上调[RB1 诱导卷曲螺旋蛋白（RB1CC1）、微管相关蛋白 1A/1B 轻链 3（MAP1LC3B）、自噬相关基因（ATG-12）]，同时降低其表观遗传调控因子；miRNA-133b、-342 和 30a。与预防性给药组相比，糖尿病肾病中咖啡酸治疗组的这些作用更为显著。基于我们的结果，我们提出咖啡酸通过抑制自噬调控 miRNA 来调节自噬途径，这可以解释其对糖尿病肾病的治疗作用。
