title: Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice.
abstract: 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 30mg/kg/i.p., or vehicle (0.9% NaCl solution) for 12days. 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 30mg/kg. Furthermore HA injection (30mg/kg) improved the altered healing pattern in diabetic animals, increased skin remodeling proteins TGF-β 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.
authors: Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, School of Medicine, University of Messina, Italy.
authors: Mariarosaria
authors: M
authors: Galeano
authors: Francesca
authors: F
authors: Polito
authors: Alessandra
authors: A
authors: Bitto
authors: Natasha
authors: N
authors: Irrera
authors: Giuseppe M
authors: GM
authors: Campo
authors: Angela
authors: A
authors: Avenoso
authors: Margherita
authors: M
authors: Calò
authors: Patrizia
authors: P
authors: Lo Cascio
authors: Letteria
authors: L
authors: Minutoli
authors: Mauro
authors: M
authors: Barone
authors: Francesco
authors: F
authors: Squadrito
authors: Domenica
authors: D
authors: Altavilla
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D006820:Hyaluronic Acid