High-molecular weight hyaluronan reduced renal PKC activation in genetically diabetic mice
High-molecular weight hyaluronan reduced renal PKC activation in genetically diabetic mice
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DOI：
10.1016/j.bbadis.2010.08.004
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发表时间：
2010-11-01
影响因子：
6.2
通讯作者：
Campo, Salvatore
中科院分区：
文献类型：
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作者：
Campo, Giuseppe M.;Avenoso, Angela;Campo, Salvatore
簇决定因子（CD44）似乎在2型糖尿病损伤的组织中起关键作用CD44刺激激活蛋白激酶C （PKC）家族，进而激活转录核因子κ B (nf - κ B)，负责炎症介质如肿瘤坏死因子α (tnf - α)、白细胞介素-6 -白细胞介素-18 （IL-18）、诱导型一氧化氮合酶（iNOS）和基质金属蛋白酶（MMPs）的表达。CD44与其配体相互作用的调控很大程度上取决于PKC。我们研究了高分子量透明质酸（HA）对遗传性糖尿病小鼠糖尿病肾病的影响。Cg-m+/+Lepr（db）小鼠从15日龄开始血浆胰岛素升高，4周时血糖水平升高。肾组织中CD44受体、蛋白激酶C β β、β β和epsilon (PKC β I、PKC β II和PKC epsilon) mRNA表达及相关蛋白产物显著升高是严重肾病的特征。在受损肾脏中也检测到nf - κ B、tnf - α、IL-6、IL-18、MMP-7和iNOS的mRNA和相关蛋白水平升高。长期每日给予高分子量HA治疗2周，可显著降低CD44。肾组织中PKC β I、PKC β II、PKC α基因表达及相关蛋白产生及tnf - α、IL-6、IL-18、MMP-7、iNOS表达及水平均下降，组织学分析证实了生化数据。然而，糖尿病患者的血液参数没有变化。这些结果表明CD44和PKC在糖尿病中发挥重要作用，高分子量HA与这些蛋白的相互作用可能会减少炎症和继发病变。(C) 2010 Elsevier B.V.
The cluster determinant (CD44) seems to play a key role in tissues injured by diabetes type 2 CD44 stimulation activates the protein kinase C (PKC) family which in turn activates the transcriptional nuclear factor kappa B (NF-kappa B) responsible for the expression of the inflammation mediators such as tumor necrosis factor alpha (TNF-alpha), interleukin-6 interleukin-18 (IL-18), inducible nitric oxide synthase (iNOS), and matrix metalloproteinases (MMPs). Regulation of CD44 interaction with its ligands depends greatly upon PKC. We investigated the effect of the treatment with high-molecular weight hyaluronan (HA) on diabetic nephropathy in genetically diabetic mice.BKS.Cg-m+/+Lepr(db) mice had elevated plasma insulin from 15 days of age and high blood sugar levels at 4 weeks. The severe nephropathy that developed was characterized by a marked increased in CD44 receptors, protein kinase C betal, betall, and epsilon (PKC beta I, PKC beta II, and PKC epsilon) mRNA expression and the related protein products in kidney tissue. High levels of mRNA and related protein levels were also detected in the damaged kidney for NF-kappa B, TNF-alpha, IL-6, IL-18, MMP-7, and iNOS.Chronic daily administration of high-molecular mass HA for 2 weeks significantly reduced CD44. PKC beta I, PKC beta II, and PKC alpha gene expression and the related protein production in kidney tissue and TNF-alpha, IL-6, IL-18, MMP-7, and iNOS expression and levels also decreased Histological analysis confirmed the biochemical data. However, blood parameters of diabetes were unchanged.These results suggest that the CD44 and PKC play an important role in diabetes and interaction of high-molecular weight HA with these proteins may reduce inflammation and secondary pathologies due to this disease (C) 2010 Elsevier B.V. All rights reserved