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Progranulin Facilitates Corneal Repair Through Dual Mechanisms of Inflammation Suppression and Regeneration Promotion
Inflammation ( IF 5.1 ) Pub Date : 2024-03-09 , DOI: 10.1007/s10753-024-01999-3
Dan Yan , Yunuo Zhang , Yuhan Huang , Weijie Ouyang

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.



中文翻译:

颗粒体蛋白前体通过抑制炎症和促进再生的双重机制促进角膜修复

角膜是眼睛重要的保护屏障;然而,它很容易受到伤害和损害,从而破坏角膜上皮和神经,引发炎症。因此,了解角膜伤口愈合的生物学效应和分子机制并识别针对这些途径的药物对于该领域的研究人员至关重要。本研究旨在探讨颗粒体蛋白前体 (PGRN) 在治疗角膜损伤中的治疗潜力。我们的研究结果表明,PGRN 通过加速角膜再上皮化和再神经支配,显着增强角膜伤口修复。培养上皮细胞和三叉神经节细胞的体外实验进一步表明,PGRN刺激角膜上皮细胞增殖并促进三叉神经节细胞轴突生长。通过RNA测序(RNA-seq)分析和其他实验技术,我们发现PGRN通过调节Wnt信号通路发挥其愈合作用,在修复上皮细胞和促进三叉神经元轴突再生中发挥着关键作用。重要的是,我们的研究强调了 PGRN 通过抑制 NF-κB 信号通路的抗炎特性,从而减少巨噬细胞的浸润。总之,我们的研究结果强调了 PGRN 通过促进角膜上皮细胞增殖、三叉神经节细胞轴突再生和抑制眼部炎症来促进角膜伤口愈合的潜力。这些结果表明 PGRN 可能会加速角膜损伤患者的愈合过程并改善视力结果。

更新日期:2024-03-09
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