Maintenance of skin integrity is crucial to avoid infections, and wound healing is a complex process that involves ROS overproduction and the activation of redox-related mechanisms. Altered wound repair is often observed in redox-imbalanced states, such as aging and diabetes (DB). In particular, DB-induced hyperglycemia promotes the build-up of methylglyoxal (MG), a pro-oxidant dicarbonyl compound that in vivo forms the so-called advanced glycation end-products (AGEs), that worsen cell damage and tissue dysfunctions. Accordingly, impaired MG detoxification, whose levels are mainly controlled by glyoxalase 1 and 2 (GLO1 and GLO2), is suspected to play a role in DB-related “difficult wounds”. However, little information is available on the function of MG metabolism in the wound healing physiology. To this aim, human keratinocytes (HaCat) were scratched and collected in a time-dependent fashion for assessing: i) gene/protein expression and enzymatic activities of GLOs; ii) levels of GSH (co-factor of GLO1); iii) levels of receptors for AGE (RAGE). In addition, ROS production, mitochondrial functional integrity and redox-modulated cell signaling pathways were also evaluated. Our preliminary results indicate that MG metabolism and other endpoints are dynamically modulated in wound healing, and this suggests that modulators of MG scavenging might be used to co-adjuvate skin lesion repair.

Role of glyoxalases in wound healing process: an in vitro study

Lombardi Francesca;Santini Silvano;Palumbo Paola;Cordone Valeria;Di Emidio Giovanna;Tatone Carla;Giuliani Maurizio;Falone Stefano;Cinque Benedetta;Amicarelli Fernanda;Cifone Maria Grazia.
2021

Abstract

Maintenance of skin integrity is crucial to avoid infections, and wound healing is a complex process that involves ROS overproduction and the activation of redox-related mechanisms. Altered wound repair is often observed in redox-imbalanced states, such as aging and diabetes (DB). In particular, DB-induced hyperglycemia promotes the build-up of methylglyoxal (MG), a pro-oxidant dicarbonyl compound that in vivo forms the so-called advanced glycation end-products (AGEs), that worsen cell damage and tissue dysfunctions. Accordingly, impaired MG detoxification, whose levels are mainly controlled by glyoxalase 1 and 2 (GLO1 and GLO2), is suspected to play a role in DB-related “difficult wounds”. However, little information is available on the function of MG metabolism in the wound healing physiology. To this aim, human keratinocytes (HaCat) were scratched and collected in a time-dependent fashion for assessing: i) gene/protein expression and enzymatic activities of GLOs; ii) levels of GSH (co-factor of GLO1); iii) levels of receptors for AGE (RAGE). In addition, ROS production, mitochondrial functional integrity and redox-modulated cell signaling pathways were also evaluated. Our preliminary results indicate that MG metabolism and other endpoints are dynamically modulated in wound healing, and this suggests that modulators of MG scavenging might be used to co-adjuvate skin lesion repair.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11697/169834
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