Effects of Matrix Metalloproteinase-9-Dependent Extracellular Matrix on Remodeling Underlie Accelerated Skin Aging in Streptozotocin-induced Diabetic Rats

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with progressive aging-related alterations in multiple organs, including the skin. Nonetheless, the specific structural and molecular changes that cause skin aging in diabetes remain poorly understood in preclinical animal models. The present study aimed to establish a rat model of T2DM-induced skin aging and to investigate the relationship between matrix metalloproteinase-9 (MMP-9) expression and dermal extracellular matrix (ECM) remodeling in diabetic skin aging. A total of 12 male Sprague-Dawley rats, aged 8-9 weeks and weighing 180-250 g, were assigned to the control and T2DM groups. Rats in the T2DM group received an 8-week high-fat diet (45% fat calories) with 40% fructose, followed by low-dose streptozotocin (25 mg/kg, IP) injection to induce diabetes. Metabolic phenotype was validated using fasting blood glucose and a 2-hour post-glucose measurement. After 16 weeks, dorsal skin was collected for histological evaluation, including measurements of epidermal/dermal thickness, collagen area, and fibroblast counts, as well as molecular analysis. The MMP-9 was measured using a sandwich enzyme-linked immunosorbent assay. Diabetic rats developed sustained hyperglycemia and increased body weight, confirming a T2DM-like metabolic phenotype. Histological analysis demonstrated a significant increase in dermal thickness and a marked reduction in dermal collagen density in diabetic skin, whereas epidermal thickness and fibroblast counts were not significantly altered. The MMP-9 concentration in diabetic dermal homogenates was elevated compared with that in the control group. The current findings demonstrated that T2DM in rats was associated with early dermal extracellular matrix remodeling, characterized by increased MMP-9 levels, decreased collagen density, and dermal thickening, suggesting an association between chronic hyperglycemia and altered dermal matrix homeostasis.