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 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.

Keywords: Diabetes; Diabetic foot ulcer; Fibroblast; Platelet-rich plasma; Wound healing; miR-192.