Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article
Abstract Background Diabetic foot ulcer (DFU) is a severe diabetic complication. Transplantation of skin substitutes, stem cells, and platelet-rich plasma (PRP) treatments are promising tools to promote ulcer healing in diabetes. An important aspect of the remodeling phase of wound healing is collag...
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BMC
2025-04-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02449-y |
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| author | Forouzan Karam Mahtab Sayadi Saeedeh Dadi Gholamreza Anani Sarab |
| author_facet | Forouzan Karam Mahtab Sayadi Saeedeh Dadi Gholamreza Anani Sarab |
| author_sort | Forouzan Karam |
| collection | DOAJ |
| description | Abstract Background Diabetic foot ulcer (DFU) is a severe diabetic complication. Transplantation of skin substitutes, stem cells, and platelet-rich plasma (PRP) treatments are promising tools to promote ulcer healing in diabetes. An important aspect of the remodeling phase of wound healing is collagen deposition. miR-192 increases the expression of COL1A2 by specifically targeting Smad-interacting protein 1 (SIP1). This study was designed to investigate the impact of combined treatment with platelet-rich plasma and fibroblast cells expressing miR-192 on the healing process of wounds using an experimental diabetic animal model. Methods After transfection of HDF cells and induction of increased miR-192 expression, relative changes in COL1A2 gene expression were determined by the RT-PCR method. Rats were randomly divided into 6 groups: non-diabetic control group, diabetic control, backbone, PRP, miR-192, and PRP + miR-192 groups. Diabetes was induced in male Wistar rats of all treated groups except non-diabetic control through a 21-day high-fat diet and an intraperitoneal injection of 40 mg/kg streptozotocin. A 10-mm skin biopsy punch was used to create two full-thickness wounds on the dorsal part of the upper body in all six groups of animals. Hematoxylin–eosin and Mason's trichrome staining were used to evaluate the wounds and analyze histological changes. Results The overexpression of miR-192 in HDF cells resulted in a significant increase in COL1A2 gene expression, which was 15.77-fold higher than the control group. PRP and pLenti-III-miR-192-GFP-expressing cells significantly increased wound closure rates, granulation tissue area, and collagen fiber density in rats, according to a histological examination. Conclusion The combined use of PRP and HDFs expressing pLenti-III-miR-192-GFP speeds up the healing of wounds by increasing collagen expression, demonstrating the efficacy of this approach in improving wound healing results. Graphical Abstract |
| format | Article |
| id | doaj-art-c4c089c771964463a41e4aaa6957c689 |
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| issn | 2047-783X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | European Journal of Medical Research |
| spelling | doaj-art-c4c089c771964463a41e4aaa6957c6892025-08-20T01:53:23ZengBMCEuropean Journal of Medical Research2047-783X2025-04-0130111510.1186/s40001-025-02449-yOverexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research articleForouzan Karam0Mahtab Sayadi1Saeedeh Dadi2Gholamreza Anani Sarab3Department of Cellular and Molecular Research Center, Birjand University of Medical SciencesDepartment of Cellular and Molecular Research Center, Birjand University of Medical SciencesDepartment of Cellular and Molecular Research Center, Birjand University of Medical SciencesDepartment of Cellular and Molecular Research Center, Birjand University of Medical SciencesAbstract Background Diabetic foot ulcer (DFU) is a severe diabetic complication. Transplantation of skin substitutes, stem cells, and platelet-rich plasma (PRP) treatments are promising tools to promote ulcer healing in diabetes. An important aspect of the remodeling phase of wound healing is collagen deposition. miR-192 increases the expression of COL1A2 by specifically targeting Smad-interacting protein 1 (SIP1). This study was designed to investigate the impact of combined treatment with platelet-rich plasma and fibroblast cells expressing miR-192 on the healing process of wounds using an experimental diabetic animal model. Methods After transfection of HDF cells and induction of increased miR-192 expression, relative changes in COL1A2 gene expression were determined by the RT-PCR method. Rats were randomly divided into 6 groups: non-diabetic control group, diabetic control, backbone, PRP, miR-192, and PRP + miR-192 groups. Diabetes was induced in male Wistar rats of all treated groups except non-diabetic control through a 21-day high-fat diet and an intraperitoneal injection of 40 mg/kg streptozotocin. A 10-mm skin biopsy punch was used to create two full-thickness wounds on the dorsal part of the upper body in all six groups of animals. Hematoxylin–eosin and Mason's trichrome staining were used to evaluate the wounds and analyze histological changes. Results The overexpression of miR-192 in HDF cells resulted in a significant increase in COL1A2 gene expression, which was 15.77-fold higher than the control group. PRP and pLenti-III-miR-192-GFP-expressing cells significantly increased wound closure rates, granulation tissue area, and collagen fiber density in rats, according to a histological examination. Conclusion The combined use of PRP and HDFs expressing pLenti-III-miR-192-GFP speeds up the healing of wounds by increasing collagen expression, demonstrating the efficacy of this approach in improving wound healing results. Graphical Abstracthttps://doi.org/10.1186/s40001-025-02449-yDiabetesDiabetic foot ulcerFibroblastmiR-192Platelet-rich plasmaWound healing |
| spellingShingle | Forouzan Karam Mahtab Sayadi Saeedeh Dadi Gholamreza Anani Sarab Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article European Journal of Medical Research Diabetes Diabetic foot ulcer Fibroblast miR-192 Platelet-rich plasma Wound healing |
| title | Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article |
| title_full | Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article |
| title_fullStr | Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article |
| title_full_unstemmed | Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article |
| title_short | Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article |
| title_sort | overexpression of mir 192 in fibroblasts accelerates wound healing in diabetic rats research article |
| topic | Diabetes Diabetic foot ulcer Fibroblast miR-192 Platelet-rich plasma Wound healing |
| url | https://doi.org/10.1186/s40001-025-02449-y |
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