School of Pharmacological Sciences, Wenzhou Medical University, Chashan University Park, Wenzhou, China; Department of Pharmacy, The Eye Hospital of Wenzhou Medical University, Wenzhou, China.
School of Pharmacological Sciences, Wenzhou Medical University, Chashan University Park, Wenzhou, China; Laboratory of Zhejiang Province for Pharmaceutical Engineering and Development of Growth Factors, Collaborative Biomedical Innovation Center of Wenzhou, Wenzhou, China.
J Biol Chem. 2023 Sep;299(9):105127. doi: 10.1016/j.jbc.2023.105127. Epub 2023 Aug 4.
Diabetic keratopathy, commonly associated with a hyperactive inflammatory response, is one of the most common eye complications of diabetes. The peptide hormone fibroblast growth factor-21 (FGF-21) has been demonstrated to have anti-inflammatory and antioxidant properties. However, whether administration of recombinant human (rh) FGF-21 can potentially regulate diabetic keratopathy is still unknown. Therefore, in this work, we investigated the role of rhFGF-21 in the modulation of corneal epithelial wound healing, the inflammation response, and oxidative stress using type 1 diabetic mice and high glucose-treated human corneal epithelial cells. Our experimental results indicated that the application of rhFGF-21 contributed to the enhancement of epithelial wound healing. This treatment also led to advancements in tear production and reduction in corneal edema. Moreover, there was a notable reduction in the levels of proinflammatory cytokines such as TNF-α, IL-6, IL-1β, MCP-1, IFN-γ, MMP-2, and MMP-9 in both diabetic mouse corneal epithelium and human corneal epithelial cells treated with high glucose. Furthermore, we found rhFGF-21 treatment inhibited reactive oxygen species production and increased levels of anti-inflammatory molecules IL-10 and SOD-1, which suggests that FGF-21 has a protective role in diabetic corneal epithelial healing by increasing the antioxidant capacity and reducing the release of inflammatory mediators and matrix metalloproteinases. Therefore, we propose that administration of FGF-21 may represent a potential treatment for diabetic keratopathy.
糖尿病性角膜病变，通常与过度活跃的炎症反应有关，是糖尿病最常见的眼部并发症之一。肽类激素成纤维细胞生长因子 21（FGF-21）已被证明具有抗炎和抗氧化特性。然而，给予重组人（rh）FGF-21 是否可能调节糖尿病性角膜病变尚不清楚。因此，在这项工作中，我们使用 1 型糖尿病小鼠和高糖处理的人角膜上皮细胞研究了 rhFGF-21 在调节角膜上皮伤口愈合、炎症反应和氧化应激中的作用。我们的实验结果表明，rhFGF-21 的应用有助于增强上皮伤口愈合。这种治疗还导致泪液产生增加和角膜水肿减轻。此外，在糖尿病小鼠角膜上皮和高糖处理的人角膜上皮细胞中，促炎细胞因子如 TNF-α、IL-6、IL-1β、MCP-1、IFN-γ、MMP-2 和 MMP-9 的水平显著降低。此外，我们发现 rhFGF-21 治疗抑制了活性氧的产生并增加了抗炎分子 IL-10 和 SOD-1 的水平，这表明 FGF-21 通过增加抗氧化能力和减少炎症介质和基质金属蛋白酶的释放，在糖尿病性角膜上皮愈合中具有保护作用。因此，我们提出给予 FGF-21 可能是治疗糖尿病性角膜病变的一种潜在方法。
