Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1812

Article

Galeano, Mariarosaria^1,2  Polito, Francesca^1,3  Bitto, Alessandra¹  Irrera, Natasha¹  Campo, Giuseppe M.³  Avenoso, Angela³  Calo, Margherita⁴  Lo Cascio, Patrizia⁵  Minutoli, Letteria¹  Barone, Mauro⁶  Squadrito, Francesco¹  Altavilla, Domenica¹ 

[1] Univ Messina, Dept Clin & Expt Med & Pharmacol, Pharmacol Sect, I-98100 Messina, Italy

[2] Univ Messina, Dept Surg Sci, Sect Plast Surg, Sch Med, I-98100 Messina, Italy

[3] Univ Messina, Dept Biochem Physiol & Nutr Sci, Sch Med, I-98100 Messina, Italy

[4] Univ Messina, Dept Expt Sci & Appl Biotechnol, Sch Vet Med, I-98100 Messina, Italy

[5] Univ Messina, Dept Food & Environm Sci, I-98100 Messina, Italy

[6] Univ Rome, Rome, Italy

关键词: Hyaluronic acid;    Diabetic mice;    Cyclins;    Transglutaminase-II;   

DOI  :  10.1016/j.bbadis.2011.03.012

来源: Elsevier

【 摘 要 】

Hyaluronic acid (HA), an essential component of the extracellular matrix, is an efficient space filler that maintains hydration, serves as a substrate for assembly of proteoglycans and is involved in wound healing. Although numerous pieces of evidence demonstrate beneficial effects in promoting wound healing in diabetes, a systemic approach has never been tested. We used an incisional wound healing model in genetically diabetic mice to test the effects of systemic injection of HA. Diabetic (n = 56) and normoglycemic (n = 56) mice were subjected to incision and randomized (8 groups of 7 animals each) to receive HA at different doses, 7.5, 15 and 30 mg/kg/i.p., or vehicle (0.9% NaCl solution) for 12 days. At the end of the experiment animals were sacrificed and skin wounds were excised for histological, biochemical and molecular analysis. Histology revealed that the most effective dose to improve wound repair and angiogenesis in diabetic mice was 30 mg/kg. Furthermore HA injection (30 mg/kg) improved the altered healing pattern in diabetic animals, increased skin remodeling proteins TGF-beta and transglutaminase-II and restored the altered expression of cyclin B1/Cdc2 complex. Evaluation of skin from diabetic animals injected with HA revealed also an increase in HA content, suggesting that systemic injection may be able to restore the reduced intracellular HA pool of diabetic mice. Finally HA markedly improved skin mechanical properties. These promising results, if confirmed in a clinical setting, may improve the care and management of diabetic patients. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

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