A20 ameliorates Aspergillus fumigatus keratitis by promoting autophagy and inhibiting NF-κB signaling

Han, Fang; Wang, Leyi; Shen, Lin; Liu, Wenhui; Li, Yangyang; Ma, Hanlin; Wu, Xinyi

doi:10.1016/j.ijbiomac.2023.127640

Cited by 4 publications

(1 citation statement)

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“…The levels of LC3 II, Beclin-1, and Atg-7 proteins showed an increase after fungal stimulation compared to those of uninfected corneas and RAW 264.7 cells. Our findings indicated that FK enhances autophagy, aligning with previous research. ,, We observed an increase in the levels of LC3 II, Beclin-1, and Atg-7 proteins in infected corneas and RAW 264.7 cells following PGRN treatment, indicating that autophagy is enhanced by PGRN in FK. Autophagy is acknowledged as a significant factor in the control of inflammation during fungal infection .…”

Section: Discussionsupporting

confidence: 91%

Progranulin Protects against Aspergillus fumigatus Keratitis by Attenuating the Inflammatory Response through Enhancing Autophagy

Qi,

Liu,

et al. 2024

ACS Infect. Dis.

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Fungal keratitis (FK) is a severe corneal condition caused by pathogenic fungi and is associated with the virulence of fungi and an excessive tissue inflammatory response. Progranulin (PGRN), functioning as a multifunctional growth factor, exerts a pivotal influence on the regulation of inflammation and autophagy. The aim of our research was to analyze the role of PGRN in Aspergillus fumigatus (A. fumigatus) keratitis. We found that PGRN expression was increased in the mouse cornea with A. fumigatus keratitis. In our experiments, corneas of mice with FK were treated with 100 ng/mL of PGRN. In vitro, RAW 264.7 cells were treated with 10 ng/mL of PGRN before A. fumigatus stimulation. The findings suggested that PGRN effectively alleviated corneal edema and decreased the expression of pro-inflammatory cytokines in mice. In stimulated RAW 264.7 cells, PGRN treatment suppressed the expression of pro-inflammatory cytokines IL-6 and TNF-α but promoted the expression of the anti-inflammatory cytokines IL-10. PGRN treatment significantly upregulated the expression of autophagy-related proteins LC3, Beclin-1, and Atg-7. 3-Methyladenine (3-MA, autophagy inhibitor) reversed the regulation of inflammatory cytokines by PGRN. In addition, our study demonstrated that PGRN also enhanced phagocytosis in RAW 264.7 cells. In summary, PGRN attenuated the inflammatory response of A. fumigatus keratitis by increasing autophagy and enhanced the phagocytic activity of RAW 264.7 cells. This showed that PGRN had a protective effect on A. fumigatus keratitis.

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