online ISSN 2415-3176
print ISSN 1609-6371
logoExperimental and Clinical Physiology and Biochemistry
J. 2026, 106(2): 48–55

Experimental medicine


Proteolytic homeostasis in skin following experimental cutaneous wounding in rats with monosodium glutamate-induced obesity

N. R. HRYTSEVУCH 1, T. V. BEREGOVA 2, L. I. KOT 2

Received: 20-07-2026

Accepted: 23-09-2026

Published: 28-09-2026

Abstract

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)

References
  1. Ahmed SK, Mohammed RA. Obesity: Prevalence, causes, consequences, management, preventive strategies and future research directions. Metabol Open. 2025;27:100375. doi.org/10.1016/j.metop.2025.100375
  2. Abad-Jiménez Z, Vezza T. Obesity: a global health challenge demanding urgent action. Biomedicines. 2025;13(2):502. doi.org/10.3390/biomedicines13020502
  3. Młynarska E, Bojdo K, Bulicz A, Frankenstein H, Gąsior M, Kustosik N, Rysz J, Franczyk B. Obesity as a multifactorial chronic disease: molecular mechanisms, systemic impact, and emerging digital interventions. Curr Issues Mol Biol. 2025;47(10):787. doi.org/10.3390/cimb47100787
  4. Zaccaron RP, Mendes C, da Costa C, Silveira PCL, Rezin GT. Skin metabolism in obesity: A narrative review. Wound Repair Regen. 2024;32(6):1022–7. doi.org/10.1111/wrr.13223
  5. Byard RW. Manifestations and etiology of cutaneous findings in cases of morbid obesity. Forensic Sci Med Pathol. 2024;20:1475–82. doi.org/10.1007/s12024-023-00721-3
  6. Musale V, Wasserman DH, Kang L. Extracellular matrix remodelling in obesity and metabolic disorders. Life Metab. 2023;2(4):load021. doi.org/10.1093/lifemeta/load021
  7. Cotterell A, Griffin M, Downer MA, Parker JB, Wan D, Longaker MT. Understanding wound healing in obesity. World J Exp Med. 2024;14(1):86898. doi.org/10.5493/wjem.v14.i1.86898
  8. Woo YR, Kim HS. Obesity, skin disorders, and the microbiota: Unraveling a complex web. J. Microbiol. 2026;64(1):e2508007.doi.org/10.71150/jm.2508007
  9. Mayorca-Guiliani AE, Leeming DJ, Henriksen K, Mortensen JH, Nielsen SH, Anstee QM, et al. ECM formation and degradation during fibrosis, repair, and regeneration. NPJ Metab Health Dis. 2025;3(1):25. doi.org/10.1038/s44324-025-00063-4
  10. Jin C, Jin Y, Ding Z, Nuch KS, Han M, Shim J, et al. Cellular and molecular mecha- nisms of wound repair: from biology to therapeutic innovation. Cells. 2025;14(23):1850. doi.org/10.3390/cells14231850
  11. Kandhwal M, Behl T, Singh S, Sharma N, Arora S, Bhatia S, et al. Role of matrix metalloproteinase in wound healing. Am J Transl Res. 2022;14(7):4391–405.
  12. Srinivas M, Yasmeen W, Ikramuddin M, Chandra AS. Predictive role of MMP-2 and MMP-9 in wound healing outcomes among critically ill patients: an observational study. Formos J Surg. 2025;58(6):250–3. doi.org/10.1097/FS9.0000000000000231
  13. Sanabria ER, Pereira MF, Dolnikoff MS, Andrade IS, Ferreira AT, Cavalheiro EA, et al. Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats. Brain Res Bull. 2002;59:47–51. doi.org/10.1016/s0361-9230(02)00837-7
  14. Azevedo PS, Gumieiro DN, Polegato BF, Pereira GJ, Silva IA, Pio SM, et al. Goldman score, but not Detsky or Lee indices, predicts mortality 6 months after hip fracture. BMC Mus- culoskelet Disord. 2017;18:134.doi.org/10.1186/s12891-017-1480-x
  15. Munilla Moran R, Stark JR. Protein digestion in early turbot larvae, Scophthalmus maximus (L.). Aquaculture 1989;8:315–27.
  16. Ostapchenko L, Savchuk O, Burlova-Vasilieva N. Enzyme electrophoresis method in analysis of active components of haemostasis system. Adv Biosci Biotechnol. 2011;2:20–6.
  17. Solomonov I, Kollet O, Sagi I. Extracellular matrix and proteolysis: mechanisms driv- ing irreversible changes and shaping cell behavior. FEBS J. 2026;293:3788-813.doi.org/10.1111/febs.70292
  18. Hrytsevich NR, Stepanova LI, Nikitina NS, Vereshchaka VV, Savchuk OM. Characteristics of biochemical indices and dynamics of healing of full-layer cut planar wounds in male and female rats with glutamate-induced obesity. Clin Exp Pathol. 2026;25(1):27–35. doi.org/10.24061/1727-4338.XXV.1.95.2026.04
  19. Hrytsevich NR, Nikitina NS, Stepanova LI, Vereshchaka VV. Concentration of metallopro- teinases in the wound bed of the skin of male rats with metabolic syndrome under the action of carbopol gel with melanin. Bukovyn Med Herald. 2026;30(1):16–23. doi.org/10.24061/2413-0737.30.1.117.2026.3
  20. Krenytska D, Rachkovska A, Liashuk I, Bakashova A, Savchuk O. The characteristic of qualitative composition of the matrix metalloproteinases in homogenates of tissues during the development of experimental obesity in the rats. Bulletin of Taras Shevchenko Kyiv National University. Biology. 2022;1(88):51–55. doi.org/10.17721/1728.2748.2022.88.51-55
  21. Krenytska D, Rachkovska A, Savchuk O. Analysis of the qualitative composition of matrix metalloproteinases in the pathogenesis of obesity induced by a high-fat diet in rats. Bulletin of Taras Shevchenko Kyiv National University. Biology. 2021;2(85):56–60. doi.org/10.17721/1728_2748.2021.85.56-60
  22. Trojanek JB. The specific role of extracellular matrix metalloproteinases in the pa- thology and therapy of hard-to-heal wounds. Acta Biochim Pol. 2023;70(4):745–50.doi.org/10.18388/abp.2020_6934


Програмування - Roman.im | QR-Code Generator