TY - JOUR

T1 - Liver Fluke-Derived Molecules Accelerate Skin Repair Processes in a Mouse Model of Type 2 Diabetes Mellitus

AU - Kovner, Anna

AU - Kapushchak, Yaroslav

AU - Zaparina, Oxana

AU - Ponomarev, Dmitry

AU - Pakharukova, Maria

N1 - This research was funded by the Russian Science Foundation, grant number 24-25-00082.

PY - 2024/11

Y1 - 2024/11

N2 - Chronic nonhealing wounds, such as diabetic ulcers, are among the most serious complications of diabetes mellitus. Consequently, the search for new therapeutic strategies remains highly relevant. Based on our previous data on acute wounds, bioactive molecules derived from the liver fluke Opisthorchis felineus hold promise as a novel approach to wound healing. The aim of this study was to investigate the wound-healing properties of excretory–secretory products (ESP) and inactivated eggs of O. felineus in a model of type 2 diabetes mellitus. Two-month-old mice of the BKS.Cg + Leprdb/+Leprdb/OlaHsd (db/db) strain were inflicted with superficial wounds of 5 mm in diameter. Mouse groups included several controls (methylcellulose as the vehicle and human recombinant PDGF as the positive control) and specific-treatment groups (ESP and inactivated O. felineus eggs). Histopathological, immunohistochemical, and RT-PCR studies using markers for M1/M2 polarization, angiogenesis, and extracellular matrix remodeling were carried out. Additionally, an image analysis of Masson’s trichrome-stained skin sections was performed. The proliferation of HaCaT cells under ESP and egg treatment was also assessed. The present study reveals a significant increase in the percentage of wound healing in ESP- and egg-treated groups, which significantly exceeded the control values after 14 days. Wound treatment with either ESP or worm eggs resulted in (i) a reduction in inflammation with a canonical M1-to-M2 polarization shift, (ii) the modulation of the vascular response, and (iii) dermal extracellular matrix remodeling. All results are comparable to those of the positive control group treated with PDGF. This study also reveals that ESP, but not O. felineus eggs, stimulated keratinocyte proliferation in vitro. The results indicate the high wound-healing potential of liver fluke bioactive molecules and open prospects for further research on these new promising therapeutic approaches.

AB - Chronic nonhealing wounds, such as diabetic ulcers, are among the most serious complications of diabetes mellitus. Consequently, the search for new therapeutic strategies remains highly relevant. Based on our previous data on acute wounds, bioactive molecules derived from the liver fluke Opisthorchis felineus hold promise as a novel approach to wound healing. The aim of this study was to investigate the wound-healing properties of excretory–secretory products (ESP) and inactivated eggs of O. felineus in a model of type 2 diabetes mellitus. Two-month-old mice of the BKS.Cg + Leprdb/+Leprdb/OlaHsd (db/db) strain were inflicted with superficial wounds of 5 mm in diameter. Mouse groups included several controls (methylcellulose as the vehicle and human recombinant PDGF as the positive control) and specific-treatment groups (ESP and inactivated O. felineus eggs). Histopathological, immunohistochemical, and RT-PCR studies using markers for M1/M2 polarization, angiogenesis, and extracellular matrix remodeling were carried out. Additionally, an image analysis of Masson’s trichrome-stained skin sections was performed. The proliferation of HaCaT cells under ESP and egg treatment was also assessed. The present study reveals a significant increase in the percentage of wound healing in ESP- and egg-treated groups, which significantly exceeded the control values after 14 days. Wound treatment with either ESP or worm eggs resulted in (i) a reduction in inflammation with a canonical M1-to-M2 polarization shift, (ii) the modulation of the vascular response, and (iii) dermal extracellular matrix remodeling. All results are comparable to those of the positive control group treated with PDGF. This study also reveals that ESP, but not O. felineus eggs, stimulated keratinocyte proliferation in vitro. The results indicate the high wound-healing potential of liver fluke bioactive molecules and open prospects for further research on these new promising therapeutic approaches.

KW - Opisthorchis felineus

KW - egg

KW - excretory–secretory product

KW - skin wound healing

KW - type 2 diabetes mellitus

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85210266913&origin=inward&txGid=35c3164f2872df506e07cd5eb5384bc3

UR - https://www.mendeley.com/catalogue/c71fcafd-6799-33da-a97d-7579f994da98/

U2 - 10.3390/ijms252212002

DO - 10.3390/ijms252212002

M3 - Article

C2 - 39596069

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 22

M1 - 12002

ER -