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Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease

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Frontiers of Medicine 2023年第4期17卷 781-795页

作者： Yu Han Yu Zhang Kelan Yuan Yaying Wu Xiuming Jin Xiaodan Huang Eye Center The Second Affiliated HospitalZhejiang University School of MedicineZhejiang Provincial Key Laboratory of OphthalmologyZhejiang Provincial Clinical Research Center for Eye DiseasesZhejiang Provincial Engineering Institute on Eye DiseasesHangzhou 310009China

Tear film hyperosmolarity plays a core role in the development of dry eye disease(DED)by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface *** this study,the mechanisms involving the hyperosmolar microenvironment,glycolysis mediating metabolic reprogramming,and pyroptosis were explored clinically,in vitro,and in *** from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes,including PKM2 and GSDMD,was significantly upregulated and that the secretion of IL-1βsignificantly *** vitro,the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells(HCECs)was used to discuss the interaction among *** hyperosmolar environment was found to greatly induce HCECs’metabolic reprogramming,which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression.2-Deoxy-d-glucose(2-DG)could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of *** vivo,2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and *** summary,our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.

关键词： dry eye disease glycolytic reprogramming pyroptosis inflammation 2-DG

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