High-molecular weight hyaluronan reduced renal PKC activation in genetically diabetic mice

被引：25

作者：

Campo, Giuseppe M. ^{[1
]}

Avenoso, Angela ^{[1
]}

Micali, Antonio ^{[2
]}

Nastasi, Giancarlo ^{[1
]}

Squadrito, Francesco ^{[3
]}

Altavilla, Domenica ^{[3
]}

Bitto, Alessandra ^{[3
]}

Polito, Francesca ^{[3
]}

Rinaldi, Maria Grazia ^{[3
]}

Calatroni, Alberto ^{[1
]}

D'Ascola, Angela ^{[1
]}

Campo, Salvatore ^{[1
]}

机构：

[1] Univ Messina, Sch Med, Dept Biochem Physiol & Nutr Sci, Policlin Univ,Sect Med Chem, I-98125 Messina, Italy

[2] Univ Messina, Sch Med, Dept Biomorphol, Policlin Univ, I-98125 Messina, Italy

[3] Univ Messina, Sch Med, Dept Clin & Expt Med & Pharmacol, Sect Pharmacol,Policlin Univ, I-98125 Messina, Italy

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2010年 / 1802卷 / 11期

关键词：

Hyaluronan; NF-kappa B; PKC; Cytokines; Diabetes; CD44; PROTEIN-KINASE-C; NF-KAPPA-B; TISSUE-INJURY; NITRIC-OXIDE; CD44; INFLAMMATION; INFILTRATION; PATHOGENESIS; NEPHROPATHY; INHIBITION;

D O I：

10.1016/j.bbadis.2010.08.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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

引用

页码：1118 / 1130

页数：13

共 56 条

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