Abstract：
BACKGROUND: Diabetic kidney disease (DKD; also known as diabetic nephropathy) is a typical complication of diabetes mellitus characterised by renal injury due to disturbances in glucose metabolism, in which renal tubular damage caused by chronic inflammation has been shown to be closely associated with the development of end-stage renal disease (ESRD). However, there are insufficient effective therapeutic agents to halt the progression of DKD.
METHODS: In the present study, we screened differential gene expression profiles associated with DKD by mining the GEO database through differential and enrichment analyses. Furthermore, systemic in vivo and in vitro experiments were designed to explore the mechanism through which the potential therapeutic agent SB-525334 improves DKD.
RESULTS: SB-525334 ameliorated DKD-induced kidney injury by regulating inflammatory cytokines (TGF-β1, IL-6, IL-10) as well as promoting the translation of M1 (iNOS) macrophage to M2 (CD206) macrophage. In addition, SB-525334 ameliorates kidney injury caused by DKD through inhibiting inflammation through regulating the expression of key proteins in the TGF-β1 /JNK and TGF-β1 /Smad signaling pathways. For studies in vitro, inflammation induced by LPS in vitro was inhibited significantly after the administration of SB-525334 through down-regulating pro-inflammatory cytokines, promoting macrophage conversion from M1 to M2, and inhibiting the activation of TGF-β1 /JNK and TGF-β1 /Smad pathways.
CONCLUSIONS: These results highlight that the target compound SB-525334 could serve as a novel potential therapeutic agent and ameliorate DKD in an inflammation-inhibiting manner.
METHODS: In the present study, we screened differential gene expression profiles associated with DKD by mining the GEO database through differential and enrichment analyses. Furthermore, systemic in vivo and in vitro experiments were designed to explore the mechanism through which the potential therapeutic agent SB-525334 improves DKD.
RESULTS: SB-525334 ameliorated DKD-induced kidney injury by regulating inflammatory cytokines (TGF-β1, IL-6, IL-10) as well as promoting the translation of M1 (iNOS) macrophage to M2 (CD206) macrophage. In addition, SB-525334 ameliorates kidney injury caused by DKD through inhibiting inflammation through regulating the expression of key proteins in the TGF-β1 /JNK and TGF-β1 /Smad signaling pathways. For studies in vitro, inflammation induced by LPS in vitro was inhibited significantly after the administration of SB-525334 through down-regulating pro-inflammatory cytokines, promoting macrophage conversion from M1 to M2, and inhibiting the activation of TGF-β1 /JNK and TGF-β1 /Smad pathways.
CONCLUSIONS: These results highlight that the target compound SB-525334 could serve as a novel potential therapeutic agent and ameliorate DKD in an inflammation-inhibiting manner.
摘要：
背景：糖尿病肾病（DKD；也称为糖尿病肾病）是糖尿病的典型并发症，其特征是由于葡萄糖代谢紊乱引起的肾损伤，其中慢性炎症引起的肾小管损伤已被证明与终末期肾病（ESRD）的发展密切相关。然而,有效的治疗药物不足以阻止DKD的进展.
方法：在本研究中，我们通过差异和富集分析挖掘GEO数据库筛选了与DKD相关的差异基因表达谱。此外，系统的体内和体外实验旨在探索潜在治疗剂SB-525334改善DKD的机制。
结果：SB-525334通过调节炎性细胞因子（TGF-β1，IL-6，IL-10）以及促进M1（iNOS）巨噬细胞的翻译改善DKD诱导的肾损伤。M2（CD206）巨噬细胞。此外,SB-525334通过调节TGF-β1/JNK和TGF-β1/Smad信号通路中关键蛋白的表达，抑制炎症反应，改善DKD引起的肾损伤。对于体外研究，给药SB-525334后，通过下调促炎细胞因子，可显著抑制LPS体外诱导的炎症反应，促进巨噬细胞M1向M2的转化,抑制TGF-β1/JNK和TGF-β1/Smad通路的激活。
结论:这些结果突出了目标化合物SB-525334可以作为新的潜在治疗剂并以抑制炎症的方式改善DKD。
方法：在本研究中，我们通过差异和富集分析挖掘GEO数据库筛选了与DKD相关的差异基因表达谱。此外，系统的体内和体外实验旨在探索潜在治疗剂SB-525334改善DKD的机制。
结果：SB-525334通过调节炎性细胞因子（TGF-β1，IL-6，IL-10）以及促进M1（iNOS）巨噬细胞的翻译改善DKD诱导的肾损伤。M2（CD206）巨噬细胞。此外,SB-525334通过调节TGF-β1/JNK和TGF-β1/Smad信号通路中关键蛋白的表达，抑制炎症反应，改善DKD引起的肾损伤。对于体外研究，给药SB-525334后，通过下调促炎细胞因子，可显著抑制LPS体外诱导的炎症反应，促进巨噬细胞M1向M2的转化,抑制TGF-β1/JNK和TGF-β1/Smad通路的激活。
结论:这些结果突出了目标化合物SB-525334可以作为新的潜在治疗剂并以抑制炎症的方式改善DKD。
