J Biol Chem
School of Pharmacological Sciences, Wenzhou Medical University, Chashan University Park, Wenzhou, China; Department of Pharmacy, The Eye Hospital of Wenzhou Medical University, Wenzhou, China; Laboratory of Zhejiang Province for Pharmaceutical Engineering and Development of Growth Factors, Collaborative Biomedical Innovation Center of Wenzhou, Wenzhou, China; Research Units of Clinical Translation of Cell Growth Factors and Diseases, Chinese Academy of Medical Science, Wenzhou, China. Electronic address:
Published: September 2023
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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10481360 | PMC |
http://dx.doi.org/10.1016/j.jbc.2023.105127 | DOI Listing |
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