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Heparanase accelerates wound angiogenesis and wound healing in mouse and rat models
Author(s) -
Zcharia Eyal,
Zilka Rachel,
Yaar Alon,
Yacoby-Zeevi Oron,
Zetser Anna,
Metzger Shula,
Sarid Ronit,
Naggi Annamaria,
Casu Benito,
Ilan Neta,
Vlodavsky Israel,
Abramovitch Rinat
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-1970com
Subject(s) - heparanase , wound healing , extracellular matrix , angiogenesis , chemistry , microbiology and biotechnology , heparan sulfate , cell migration , neovascularization , granulation tissue , immunology , cell , cancer research , biology , biochemistry
Orchestration of the rapid formation and reorganization of new tissue observed in wound healing involves not only cells and polypeptides but also the extracellular matrix (ECM) microenvironment. The ability of heparan sulfate (HS) to interact with major components of the ECM suggests a key role for HS in maintaining the structural integrity of the ECM. Heparanase, an endoglycosidase‐degrading HS in the ECM and cell surface, is involved in the enzymatic machinery that enables cellular invasion and release of HS‐bound polypeptides residing in the ECM. Bioavailabilty and activation of multitude mediators capable of promoting cell migration, proliferation, and neovascularization are of particular importance in the complex setting of wound healing. We provide evidence that heparanase is normally expressed in skin and in the wound granulation tissue. Heparanase stimulated keratinocyte cell migration and wound closure in vitro. Topical application of recombinant heparanase significantly accelerated wound healing in a flap/punch model and markedly improved flap survival. These heparanase effects were associated with enhanced wound epithelialization and blood vessel maturation. Similarly, a marked elevation in wound angiogenesis, evaluated by MRI analysis and histological analyses, was observed in heparanase‐overexpressing transgenic mice. This effect was blocked by a novel, newly developed, heparanase‐inhibiting glycol‐split fragment of heparin. These results clearly indicate that elevation of heparanase levels in healing wounds markedly accelerates tissue repair and skin survival that are mediated primarily by an enhanced angiogenic response.—Zcharia, E., Zilka, R., Yaar, A., Yacoby‐Zeevi, O., Zetser, A., Metzger, S., Sarid, R., Naggi, A., Casu, B., Ilan, N., Vlodavsky, I., Abramovitch, R. Heparanase accelerates wound angiogenesis and wound healing in mouse and rat models. FASEB J. 19, 211–221 (2005)