Department of Integrated Chinese and Western Medicine II, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China.
Department of Neurology IV, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China.
J Cell Biochem. 2019 Mar;120(3):3467-3473. doi: 10.1002/jcb.27621. Epub 2018 Nov 30.
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)-1β, IL-6, tumor necrosis factor α, 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 κB (NF-κB) 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-κB 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-κB pathway was involved in the function of nobiletin.
糖尿病肾病（DN）是一种慢性糖尿病并发症，也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 DN 的发病机制中起重要作用。有证据表明，川陈皮素具有抗炎作用，并在糖尿病中起关键作用；然而，其在 DN 中的作用尚不清楚。在本研究中，我们揭示了川陈皮素在高糖诱导的肾小球系膜细胞炎症和 ECM 积聚中的作用。川陈皮素处理显著阻断了高糖诱导的肾小球系膜细胞增殖。川陈皮素处理显著抑制了炎症细胞因子的分泌，包括白细胞介素（IL）-1β、IL-6、肿瘤坏死因子α和单核细胞趋化蛋白 1在高糖诱导的肾小球系膜细胞中。此外，川陈皮素暴露于高糖诱导的肾小球系膜细胞可通过抑制 ECM 相关蛋白型 4 胶原和纤维连接蛋白的表达，显著减少 ECM 积聚。此外，川陈皮素通过抑制信号转导和转录激活因子 3（STAT3）抑制核因子 κB（NF-κB）通路的激活。STAT3 的过表达逆转了川陈皮素对高糖诱导的肾小球系膜细胞增殖、炎症、ECM 积聚和 NF-κB 通路激活的作用。因此，我们的结果表明，川陈皮素通过抑制炎症和 ECM 积聚在高糖诱导的肾小球系膜细胞中发挥作用，STAT3/NF-κB 通路参与了川陈皮素的功能。
