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Progranulin Facilitates Corneal Repair Through Dual Mechanisms of Inflammation Suppression and Regeneration Promotion

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Abstract

The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects modulating Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Ophthalmology, the Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Guizhou, Xiamen, China

    Dan Yan, Yunuo Zhang, Yuhan Huang & Weijie Ouyang

  2. Xiamen University affiliated Xiamen Eye Center, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Fujian Engineering and Research Center of Eye Regenerative Medicine, Xiamen, China

    Dan Yan, Yunuo Zhang, Yuhan Huang & Weijie Ouyang

  3. Department of Ophthalmology, Xiang’an Hospital of Xiamen University, Xiamen, China

    Dan Yan, Yunuo Zhang, Yuhan Huang & Weijie Ouyang

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Dan Yan made substantial contributions to the conception, acquisition, analysis, design of the work; Yunuo Zhang revised it critically for important intellectual content; Yuhan Huang helped write the manuscript. Weijie Ouyang approved the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors reviewed the manuscript.

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Yan, D., Zhang, Y., Huang, Y. et al. Progranulin Facilitates Corneal Repair Through Dual Mechanisms of Inflammation Suppression and Regeneration Promotion. Inflammation (2024). https://doi.org/10.1007/s10753-024-01999-3

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