Endothelial Cell Responses to Photobiomodulation Treatments in Diabetic Wounds Are Mediated via Concerted PDGF, VEGF and TGF-β Signalling.

IF 3.4 3区 医学 Q2 CELL BIOLOGY
Victória Regina da Silva Oliveira, Ridham Varsani, Mahjuba Zehra, Camila Squarzoni Dale, Praveen Arany
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Abstract

Diabetic ulcers resulting from neural and vascular perturbations represent a large proportion of non-traumatic lower limb amputations. Conventional treatments have limited efficacy. The non-invasive use of low-dose light treatments, termed photobiomodulation (PBM), has shown therapeutic benefits in diabetic patients. This study aimed to explore the response of endothelial cells to PBM treatment under hyperglycemic conditions in vitro. The major goal was to gain mechanistic insights into the biological effects of low-dose light, with the aim of optimising clinical treatment strategies. Therefore, human umbilical vein endothelial cells were exposed to hyperglycemic conditions (150-300 mM glucose) and incubated at 37°C with 5% CO2 for 24 h. The cells were then treated with low-dose light (660 nm, CW, 10 mW/cm2, 200 s and 0.84 Einstein). Cell responses were assessed through key signalling pathways, evaluating proliferation using the AlamarBlue assay, migration through the wound scratch assay and angiogenesis via the tubulogenesis assay, with assessments after 24 or 48 h. Data were analysed using one-way ANOVA followed by Tukey's post-test. Data showed that PBM treatments performed under controlled thermal conditions significantly improved endothelial cell proliferation, migration and tubulogenesis under hyperglycemic conditions. Crosstalk among platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-β1) signalling modulated these critical responses involving matrix metalloproteinases (MMP-2 and 9) activity. These findings showed that PBM treatments exert positive endothelial cell responses under hyperglycemic conditions that could contribute to improved diabetic wound healing. These observations provide mechanistic insights into enabling PBM as a novel and adjacent therapy for diabetic wound management.

内皮细胞对光生物调节治疗的反应是通过PDGF、VEGF和TGF-β信号传导介导的。
由神经和血管紊乱引起的糖尿病溃疡在非创伤性下肢截肢中占很大比例。常规治疗的效果有限。无创使用低剂量光治疗,称为光生物调节(PBM),已显示出治疗糖尿病患者的益处。本研究旨在探讨体外高血糖条件下内皮细胞对PBM处理的反应。主要目标是获得低剂量光的生物学效应的机制见解,以优化临床治疗策略。因此,将人脐静脉内皮细胞暴露在高血糖条件下(150-300 mM葡萄糖),并在37°C和5% CO2下孵育24小时。然后用低剂量光(660 nm,连续波,10 mW/cm2, 200 s, 0.84 Einstein)处理细胞。通过关键信号通路评估细胞反应,使用AlamarBlue试验评估增殖,通过伤口划伤试验评估迁移,通过小管生成试验评估血管生成,并在24或48小时后评估。数据分析采用单因素方差分析,随后进行Tukey后验。数据显示,在受控热条件下进行PBM治疗可显著改善高血糖条件下内皮细胞的增殖、迁移和小管形成。血小板衍生生长因子(PDGF)、血管内皮生长因子(VEGF)和转化生长因子-β (TGF-β1)信号之间的串扰调节了这些涉及基质金属蛋白酶(MMP-2和9)活性的关键反应。这些发现表明,在高血糖条件下,PBM治疗可以发挥积极的内皮细胞反应,有助于改善糖尿病伤口愈合。这些观察结果为使PBM成为糖尿病伤口管理的一种新的邻近治疗方法提供了机制见解。
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来源期刊
Wound Repair and Regeneration
Wound Repair and Regeneration 医学-皮肤病学
CiteScore
5.90
自引率
3.40%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Wound Repair and Regeneration provides extensive international coverage of cellular and molecular biology, connective tissue, and biological mediator studies in the field of tissue repair and regeneration and serves a diverse audience of surgeons, plastic surgeons, dermatologists, biochemists, cell biologists, and others. Wound Repair and Regeneration is the official journal of The Wound Healing Society, The European Tissue Repair Society, The Japanese Society for Wound Healing, and The Australian Wound Management Association.
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