Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway.
Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway.
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Kirenol 通过调节 TGF-β/Smads 和 NF-κB 信号通路减轻糖尿病肾病。
DOI：
10.1080/13880209.2022.2112239
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发表时间：
2022-12
影响因子：
3.8
通讯作者：
Wu, Suzhen
中科院分区：
文献类型：
--
作者：
Li, Jialin;Zhang, Jiawen;Yang, Meng;Huang, Xiaocui;Zhang, Meng;Fang, Xiansong;Wu, Suzhen
Kirenol具有抗炎、抗纤维化和抗关节炎的作用。然而，其对糖尿病肾病（DN）的肾脏保护作用尚未得到评价。本研究探讨奇雷诺对DN的肾脏保护作用，并阐明其可能的机制。用20 µM kirenol和10 ng/mL人重组TGF-β1或30 mM葡萄糖处理系膜细胞24 h。然后收获细胞以测定靶基因或蛋白的表达。30只C57 BL/6 J雄性小鼠经高脂饮食和链脲佐菌素注射诱导糖尿病，然后随机分为3组（n = 10）：溶媒组（DM组）、2 mg/kg奇雷诺组（DM +奇雷诺组）和200 mg/kg二甲双胍组（Met组），口服给药3个月。健康对照组（Con，n = 10）。与DM组相比，kirenol处理降低了Smad 2/3和NF-κB的磷酸化水平（0.64和0.43倍），降低了FN和Col IV的积累（0.58和0.35倍），而且在体内和体外kirenol处理后IκBα的表达均恢复至正常水平。在kirenol处理后，IL-6表达在体外和体内分别降低0.35和0.57倍，TNF-α表达降低0.34和0.46倍。此外，kirenol减轻肾小球基底膜厚度和足突融合。Kirenol可通过下调TGF-β/Smads和NF-κB信号通路减轻DN。我们的研究为kirenol治疗DN提供了一个潜在的机制。
Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated. This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms. The mesangial cells were treated with 20 µM kirenol and 10 ng/mL human recombinant TGF-β1 or 30 mM glucose for 24 h. Then the cells were harvested to assay the expression of the target genes or proteins. Thirty C57BL/6J male mice were given high-fat diet with streptozotocin injection to induce diabetes and then were randomized into three groups (n = 10): vehicle administration (DM group), 2 mg/kg kirenol (DM + kirenol group) and 200 mg/kg metformin (Met group) for 3 months, orally. A healthy group (Con, n = 10) was included as the control. Compared to the DM group, kirenol treatment decreased the phosphorylation of Smad2/3 and NF-κB (0.64- and 0.43-fold) as well as the accumulation of FN and Col IV (0.58- and 0.35-fold); moreover, the expression of IκBα was restored to normal level by kirenol treatment both in vivo and in vitro. After kirenol treatment, IL-6 expression was decreased 0.35- and 0.57-fold, and TNF-α expression was decreased 0.34- and 0.46-fold, in vitro and in vivo, respectively. Furthermore, kirenol alleviated the glomerular basement membrane thickness and foot process fusion. Kirenol could alleviate DN by downregulating the TGF-β/Smads and the NF-κB signal pathway. Our study provides a potential mechanism for the treatment of DN with kirenol.
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