Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, India.
Exp Dermatol. 2024 Oct;33(10):e15189. doi: 10.1111/exd.15189.
Wound healing is a complex biological process crucial for tissue repair, wherein keratinocytes play a pivotal role in initiating, sustaining and completing the cascade. Various local and systemic factors, such as lifestyle, age metabolic disorders and vascular insufficiency, can influence this process, and in the context of diabetic wounds, disrupted biological mechanisms, including inflammation, tissue hypoxia, decrease in collagen production along with increased oxidative stress and keratinocyte dysfunction, contribute to delayed healing. During re-epithelialisation, keratinocytes undergo rapid multiplication and migration, forming a dense hyperproliferative epithelial layer that restores the epidermal barrier. Nuclear factor-erythroid 2-related factor (Nrf2), a vital transcription factor, emerges as a central regulator in managing antioxidant proteins and detoxifying enzymes, serving as a guardian against elevated reactive oxygen species (ROS) levels during stress. Nrf2 also orchestrates angiogenesis and anti-inflammatory responses crucial for wound repair. Studies demonstrate that under high-glucose conditions, Nrf2 activation promotes wound healing by enhancing cell proliferation and migration while reducing apoptosis. Nrf2 activators stimulate endogenous antioxidant production, thereby mitigating oxidative stress. Furthermore, Nrf2 upregulation is associated with decreased expression of cytokines such as TNF-α and IL- 6. Recent research underscores the potential of bioactive molecules, including dietary polyphenols, traditional medicinal compounds and pharmacological agents, in activating Nrf2 and preventing diseases such as diabetes due to their robust antioxidative properties. This review aims to investigate the activation of Nrf2 by these bioactive molecules in cultured keratinocytes and animal models, elucidating the key molecular regulatory mechanisms involved in alleviating oxidative stress and facilitating the diabetic wound healing process. Understanding these complex pathways may offer insights into novel therapeutic strategies for enhanced wound healing in diabetes-associated complications.
伤口愈合是组织修复的一个复杂的生物学过程，在此过程中角质细胞在启动、维持和完成级联反应中起着关键作用。各种局部和全身因素，如生活方式、年龄、代谢紊乱和血管功能不全，都可以影响这个过程，而在糖尿病伤口的情况下，包括炎症、组织缺氧、胶原蛋白生成减少以及氧化应激和角质细胞功能障碍增加在内的生物学机制的破坏，导致愈合延迟。在再上皮化过程中，角质细胞经历快速增殖和迁移，形成一层致密的过度增殖的上皮层，恢复表皮屏障。核因子-红细胞 2 相关因子（Nrf2）作为一种重要的转录因子，是管理抗氧化蛋白和解毒酶的核心调节剂，在应激时充当防止活性氧（ROS）水平升高的守护者。Nrf2 还协调血管生成和抗炎反应，这对伤口修复至关重要。研究表明，在高糖条件下，Nrf2 的激活通过增强细胞增殖和迁移，同时减少细胞凋亡，促进伤口愈合。Nrf2 激活剂刺激内源性抗氧化剂的产生，从而减轻氧化应激。此外，Nrf2 的上调与 TNF-α 和 IL-6 等细胞因子的表达减少有关。最近的研究强调了生物活性分子（包括膳食多酚、传统药用化合物和药理学制剂）的潜力，它们通过其强大的抗氧化特性，激活 Nrf2 并预防糖尿病等疾病。本综述旨在研究这些生物活性分子在培养的角质细胞和动物模型中对 Nrf2 的激活作用，阐明涉及缓解氧化应激和促进糖尿病伤口愈合过程的关键分子调节机制。了解这些复杂的途径可能为糖尿病相关并发症的增强伤口愈合提供新的治疗策略提供思路。
