{"title":"在成纤维细胞中过表达 miR-192 可加速糖尿病大鼠的伤口愈合:研究文章。","authors":"Forouzan Karam, Mahtab Sayadi, Saeedeh Dadi, Gholamreza Anani Sarab","doi":"10.1186/s40001-025-02449-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":11949,"journal":{"name":"European Journal of Medical Research","volume":"30 1","pages":"239"},"PeriodicalIF":2.8000,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969854/pdf/","citationCount":"0","resultStr":"{\"title\":\"Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article.\",\"authors\":\"Forouzan Karam, Mahtab Sayadi, Saeedeh Dadi, Gholamreza Anani Sarab\",\"doi\":\"10.1186/s40001-025-02449-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":11949,\"journal\":{\"name\":\"European Journal of Medical Research\",\"volume\":\"30 1\",\"pages\":\"239\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-04-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969854/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s40001-025-02449-y\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40001-025-02449-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
背景:糖尿病足溃疡是一种严重的糖尿病并发症。皮肤替代品移植、干细胞和富血小板血浆(PRP)治疗是促进糖尿病溃疡愈合的有希望的工具。伤口愈合的重塑阶段的一个重要方面是胶原沉积。miR-192通过特异性靶向smad相互作用蛋白1 (SIP1)来增加COL1A2的表达。本研究旨在探讨富血小板血浆和表达miR-192的成纤维细胞联合治疗对实验性糖尿病动物模型伤口愈合过程的影响。方法:转染HDF细胞,诱导miR-192表达升高后,采用RT-PCR法测定COL1A2基因表达的相对变化。大鼠随机分为6组:非糖尿病对照组、糖尿病对照组、骨干组、PRP组、miR-192组、PRP + miR-192组。除非糖尿病对照组外,所有治疗组雄性Wistar大鼠均通过21 d高脂饮食和40 mg/kg链脲佐菌素腹腔注射诱导糖尿病。在所有六组动物中,使用10毫米皮肤活检穿孔在上肢背部创造两个全层伤口。采用苏木精-伊红染色和梅森三色染色对创面进行评价和组织学变化分析。结果:在HDF细胞中过表达miR-192导致COL1A2基因表达显著增加,比对照组高15.77倍。根据组织学检查,PRP和表达pif - iii - mir -192- gfp的细胞显著增加了大鼠的伤口愈合率、肉芽组织面积和胶原纤维密度。结论:PRP与表达plenti3 - mir -192- gfp的HDFs联合使用可通过增加胶原表达加速创面愈合,证明该方法改善创面愈合效果的有效性。
Overexpression of miR-192 in fibroblasts accelerates wound healing in diabetic rats: research article.
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.
期刊介绍:
European Journal of Medical Research publishes translational and clinical research of international interest across all medical disciplines, enabling clinicians and other researchers to learn about developments and innovations within these disciplines and across the boundaries between disciplines. The journal publishes high quality research and reviews and aims to ensure that the results of all well-conducted research are published, regardless of their outcome.