Background. Obesity contributes to the pathogenesis of numerous skin diseases and impairs wound healing by disrupting extracellular matrix homeostasis and tissue remodeling. However, the state of the skin proteolytic system following wound healing under obese conditions remains poorly understood. This study aimed to evaluate alterations in the skin proteolytic system following wound healing in rats with and without monosodium glutamate-induced (MGI) obesity. Materials and methods. Forty male outbred rats were divided into four groups (n = 10): Intact control, MGI obesity (MGI-Ob), Wound, and MGI-Ob + Wound. Full-thickness excisional skin wounds were created in the Wound and MGI-Ob + Wound groups. Following complete macroscopic wound closure, skin samples were collected from the healed wound site. Total proteolytic activity and enzymatic activities of metal-dependent and serine proteases were determined using selective inhibition. Gelatin zymography was performed to characterize qualitative changes in the gelatinolytic protease profile. Results. Total proteolytic activity progressively increased in animals of all experimental groups, reaching the highest level in rats with MGI obesity following experimental wound healing. Serine proteases contributed more substantially to the overall increase in proteolytic activity than metal-dependent proteases. Gelatin zymography revealed progressive remodeling of the gelatinolytic protease profile, characterized by a shift from the predominance of putative active MMP-13 in intact control rats to low-molecular-weight gelatinolytic fragments following wound healing under obese conditions. Conclusion. Experimental obesity was associated with persistent activation of the skin proteolytic system and qualitative remodeling of the gelatinolytic protease profile following wound closure, indicating dysregulation of proteolytic homeostasis during the late phase of wound healing.

Keywords: obesity, cutaneous wound healing, proteolytic homeostasis, proteolytic activity, serine proteases, metal-dependent proteases, matrix metalloproteinases, gelatin zymography, skin, rats

Full text: PDF (Eng)