Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation and inflammation in rat mesangial cells: Involvement of NF-κB signaling pathway
Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation and inflammation in rat mesangial cells: Involvement of NF-κB signaling pathway
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DOI：
10.1016/j.mce.2010.07.023
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Huang, Heqing
中科院分区：
文献类型：
--
作者：
Jiang, Qin;Liu, Peiqing;Huang, Heqing
背景资料：本课题组前期研究表明，小檗碱能改善糖尿病肾病（DN）大鼠和小鼠的肾功能，抑制高糖培养的大鼠肾小球系膜细胞（MC）细胞外基质（ECM）成分纤维连接蛋白（FN）的表达。然而，其分子机制尚未完全阐明。目的：为了探讨小檗碱治疗ON的可能机制，我们研究了小檗碱对脂多糖（LPS）诱导的核因子-κ B的影响（NF-κ B B）活化及其下游炎症介质，如细胞间粘附分子-1（ICAM-1）、转化生长因子-β 1方法：采用MTT法检测MCs增殖活性。Western blot和共聚焦显微镜检测NF-κ B B的活化。结果：小檗碱可明显抑制LPS诱导的MCs增殖，抑制NF-κ B B核转位，并抑制ICAM-1、TGF-β 1、iNOS和FN的蛋白表达。小檗碱通过抑制NF-κ B B信号通路的激活及其下游炎症介质的蛋白表达，显著抑制LPS诱导的MC增殖和FN表达。小檗碱对DN的改善作用可能与其抑制NF-κ B B信号通路有关，而与其降糖作用无关。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Background: Our previous studies demonstrated that berberine could improve the renal function in rats and mice with diabetic nephropathy (DN) and inhibit extracellular matrix (ECM) component, fibronectin (FN) expression in rat mesangial cells (MCs) cultured under high glucose. However, the molecular mechanisms have not been fully elucidated.Objective: To explore the potential mechanisms of berberine in the treatment of ON, we investigated the effects of berberine on lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-kappa B) activation and its downstream inflammatory mediators, such as intercellular adhesion molecule-1 (ICAM-1), transforming growth factor-beta 1 (TGF-beta 1), inducible nitric oxide synthase (iNOS) and fibronectin (FN) protein expression in rat MCs.Method: Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The activation of NF-kappa B was detected by Western blot and confocal microscopy. The protein levels of ICAM-1, TGF-beta 1, iNOS and FN in rat MCs were detected by Western blot.Results: Our results revealed that berberine significantly suppressed LPS-induced cell proliferation and inhibited LPS-induced NF-kappa B nuclear translocation in MCs, as well as protein expression of ICAM-1, TGF-beta 1, iNOS and FN.Conclusion: Berberine significantly repressed LPS-induced cell proliferation and FN expression in rat MCs through inhibiting the activation of NF-kappa B signaling pathway and protein expression of its downstream inflammatory mediators. The ameliorative effects of berberine on DN might be associated with this inhibition effect on NF-kappa B signaling pathway which was independent of its hypoglycemic effect. (C) 2010 Elsevier Ireland Ltd. All rights reserved.