Nobiletin suppresses high-glucose-induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF-κB pathway
Nobiletin suppresses high-glucose-induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF-κB pathway
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DOI：
10.1002/jcb.27621
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发表时间：
2019-03-01
影响因子：
4
通讯作者：
Jia, Kui
中科院分区：
文献类型：
--
作者：
Liu, Zhenzhou;Han, Yanru;Jia, Kui
糖尿病肾病是一种慢性糖尿病的并发症，是全世界终末期肾病的主要原因。炎症和细胞外基质(ECM)积聚在糖尿病肾病的发病机制中起重要作用。有证据表明，nobiletin具有抗炎作用，并在糖尿病中发挥关键作用；然而，其在糖尿病肾病中的作用尚不清楚。在目前的研究中，我们揭示了nobiletin参与了高糖诱导的肾小球系膜细胞炎症和ECM积聚。诺比莱汀可显著抑制高糖诱导的肾小球系膜细胞增殖。诺比莱汀可显著抑制高糖诱导的肾小球系膜细胞炎症细胞因子的分泌，包括IL-1β、IL-6、肿瘤坏死因子α和单核细胞趋化蛋白1。此外，将nobiletin暴露于高糖诱导的肾小球系膜细胞，通过抑制ECM相关蛋白4型胶原和纤维连接蛋白的表达，显著减少了ECM的积聚。此外，nobiletin可通过抑制信号转导和转录激活因子3(STAT3)抑制核因子-kappaB(NF-kappa B)途径的激活。过表达的STAT3逆转了nobiletin对高糖诱导的肾小球系膜细胞增殖、炎症、ECM积聚和NF-kappa B途径激活的影响。因此，我们的结果提示nobiletin通过抑制炎症和ECM积聚在高糖诱导的肾小球系膜细胞中发挥作用，而STAT3/NF-kappa B通路参与了nobiletin的作用。
Diabetic nephropathy (DN) is a complication of chronic diabetes and the main cause of end-stage renal disease all over the world. Inflammation and extracellular matrix (ECM) accumulation play important roles in the pathogenesis of DN. Evidence suggested that nobiletin acts anti-inflammatory role and plays a critical role in diabetes; however, its role in DN remains unclear. In the current study, we promulgated the nobiletin involved in high-glucose-induced glomerular mesangial cell inflammation and ECM accumulation. Nobiletin treatment significantly abrogated high-glucose-induced glomerular mesangial cell proliferation. Nobiletin treatment markedly suppressed inflammation cytokine secretion, including interleukin (IL)-1 beta, IL-6, tumor necrosis factor alpha, and monocyte chemoattractant protein 1 in high-glucose-induced glomerular mesangial cell. Also, exposed nobiletin to high-glucose-induced glomerular mesangial cell considerably reduced ECM accumulation through inhibited ECM-associated protein type 4 collagen and fibronectin expression. Furthermore, nobiletin treatment abolished nuclear factor kappa B (NF-kappa B) pathway activation through signal transducer and activator of transcription 3 (STAT3) inhibition. Overexpression STAT3 reversed the effects of nobiletin on high-glucose-induced glomerular mesangial cell proliferation, inflammation, ECM accumulation, and NF-kappa B pathway activation. Hence, our results suggest that nobiletin play roles in high-glucose-induced glomerular mesangial cells through inhibiting inflammation and ECM accumulation, and the STAT3/NF-kappa B pathway was involved in the function of nobiletin.