Hyaluronidase modulates inflammatory response and accelerates the cutaneous wound healing

• Published in: PloS one Vol. 9; no. 11; p. e112297
• Main Authors: Fronza, Marcio, Caetano, Guilherme F, Leite, Marcel N, Bitencourt, Claudia S, Paula-Silva, Francisco W G, Andrade, Thiago A M, Frade, Marco A C, Merfort, Irmgard, Faccioli, Lúcia H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-11-2014; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Biology; Biology and Life Sciences; Cell adhesion & migration; Cell Movement; Cell number; Cell Proliferation; Collagen; Collagen - drug effects; Cytokines; Cytokines - drug effects; Cytokines - metabolism; Dermatology; Drugs; Edema; Eicosanoids; Eicosanoids - metabolism; Extracellular matrix; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - physiology; Gene expression; Granulation; Granulation Tissue - drug effects; Granulation Tissue - growth & development; Growth factors; Homeostasis; Hyaluronic acid; Hyaluronoglucosaminidase - pharmacology; Inflammation; Inflammation - immunology; Inflammatory response; Infusion fluids; Laboratories; Male; Medicine and Health Sciences; Mice; Peroxisome proliferator-activated receptors; Peroxisome Proliferator-Activated Receptors - drug effects; Physiology; Rats; Rats, Wistar; Receptors; Rodents; Skin; Skin Physiological Phenomena; Uranium; Wound healing; Wound Healing - drug effects; Wound Healing - physiology; Brazil; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112297

Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders.