Psoralen alleviates high glucose-induced HK-2 cell injury by inhibition of Smad 2 signaling via upregulation of microRNA 874
Psoralen alleviates high glucose-induced HK-2 cell injury by inhibition of Smad 2 signaling via upregulation of microRNA 874
复制标题
补骨脂素通过上调 microRNA 抑制 Smad 2 信号传导来减轻高葡萄糖诱导的 HK-2 细胞损伤 874
DOI：
10.1186/s40360-020-00434-1
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发表时间：
2020-07-22
影响因子：
2.9
通讯作者：
Zheng, Donghui
中科院分区：
文献类型：
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作者：
Lin, Yongtao;Zhong, Lili;Zheng, Donghui
背景糖尿病肾病（diabetic nephropathy，DN）是糖尿病患者死亡的主要原因.减缓其发病率的新治疗方法仍然缺乏。补骨脂素是补骨脂的主要活性成分。(PCL)它被用来治疗许多疾病。本研究采用体外DN模型，观察葛根素对高糖（HG）刺激的人肾HK-2细胞（48 h）的作用，并采用细胞活力测定和免疫荧光法观察葛根素对高糖刺激的人肾HK-2细胞的作用。RT-qPCR检测细胞中miRNA的表达。进一步通过细胞转染、凋亡检测、炎性细胞因子检测和Western blot等方法探讨其分子机制。同时，葛根素还能抑制HG诱导的HK-2细胞分泌炎性细胞因子和细胞外基质（ECM）的积聚。另外，peptide可显著上调HK-2细胞中miR-874的表达。Western blot结果显示，葛根素可通过上调miR-874的表达，逆转HG诱导的TLR-4/NF-κB和Smad 2表达的增加。结论葛根素可通过上调miR-874的表达，减轻HG诱导的HK-2细胞损伤。此外，人参皂甙可逆转HG诱导的TLR-4/NF-κB和Smad 2表达的增加。因此，补骨脂素可能作为治疗DN的药物。
BackgroundDiabetic nephropathy (DN) causes the vast proportion of excess mortality for patients with diabetes. Novel therapeutic approaches slowing down its incidence is still lacking. Psoralen is the major active ingredient ofPsoralea corylifolia Linn.(PCL), which was used to treat a number of diseases. In this study, we aimed to investigate whether psoralen could alleviate DN using in vitro model.MethodsCell viability assay and immunofluorescence were used to evaluate the effect of psoralen on high glucose (HG)-stimulated human kidney HK-2 cells (48 h). RT-qPCR was used to detect the expressions of miRNA in cells. Cell transfection, apoptosis assay, inflammatory cytokines detection and Western blot were further performed to explore the underlying molecular mechanisms.ResultsHG-induced toxicity of HK-2 cells was alleviated by psoralen. Meanwhile, the secretion of inflammatory cytokines and extracellular matrix (ECM) accumulation induced by HG in HK-2 cells were also decreased by psoralen. In addition, the expression of miR-874 in HK-2 cells was significantly upregulated by psoralen. Western blot assays indicated that psoralen could reverse HG-induced increase of TLR-4/NF-κB and Smad2 via upregulation of miR-874.ConclusionThis study demonstrated that psoralen could significantly alleviate HG-induced HK-2 cell injury via upregulation of miR-874. In addition, HG-induced increase of TLR-4/NF-κB and Smad2 was revered by psoralen. Therefore, psoralen might serve as an agent for the treatment of DN.