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

Mulyaningsih, Ruri Eka Maryam and Kartinah, Neng Tine and Prijanti, Ani Retno and Nugroho, Christian Marco Hadi and Krisnamurti, Desak Gede Budi (2026) Effects of Matrix Metalloproteinase-9-Dependent Extracellular Matrix on Remodeling Underlie Accelerated Skin Aging in Streptozotocin-induced Diabetic Rats. World's Veterinary Journal. 127 - 138. ISSN 23224568

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Abstract

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. © The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Item Type:	Article
Keywords:	Collagen; Dermal extracellular matrix; Matrix metalloproteinase-9; Rat; Skin aging; Type 2 diabetes mellitus
Subjects:	S Agriculture > SF Animal culture
Divisions:	World's Veterinary Journal (WVJ)
Page Range:	127 - 138
Journal or Publication Title:	World's Veterinary Journal
Journal Index:	Scopus
Volume:	16
Number:	1
Publisher:	Scienceline Publication
Identification Number:	https://doi.org/10.54203/scil.2026.wvj12
ISSN:	23224568
Depositing User:	Dr. Alireza Sadeghi
URI:	https://eprints.science-line.com/id/eprint/1742

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