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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

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Frontiers of Medicine  2023, Vol. 17 Issue (4): 781-795   https://doi.org/10.1007/s11684-023-0986-x
  本期目录
Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease
Yu Han, Yu Zhang, Kelan Yuan, Yaying Wu, Xiuming Jin, Xiaodan Huang()
Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou 310009, China
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Abstract：

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 epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data 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-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The 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 macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis.
Key words： dry eye disease    glycolytic reprogramming    pyroptosis    inflammation    2-DG
收稿日期: 2022-03-06      出版日期: 2023-10-12
Corresponding Author(s): Xiaodan Huang   
 引用本文:   
. [J]. Frontiers of Medicine, 2023, 17(4): 781-795.
Yu Han, Yu Zhang, Kelan Yuan, Yaying Wu, Xiuming Jin, Xiaodan Huang. Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial cells in dry eye disease. Front. Med., 2023, 17(4): 781-795.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-023-0986-x
https://academic.hep.com.cn/fmd/CN/Y2023/V17/I4/781
Gene Forward primer sequence Reverse primer sequence
Human-NLRP3 5′-GATCTTCGCTGCGATCAACAG-3′ 5′-CGTGCATTATCTGAACCCCAC-3′
Human-caspase-1 5′-TTTCCGCAAGGTTCGATTTTCA-3′ 5′-GGCATCTGCGCTCTACCATC-3′
Human-GSDMD 5′-GTGTGTCAACCTGTCTATCAAGG-3′ 5′-CATGGCATCGTAGAAGTGGAAG-3′
Human-IL-1β 5′-ATGATGGCTTATTACAGTGGCAA-3′ 5′-GTCGGAGATTCGTAGCTGGA-3′
Human-HK1 5′-GCTCTCCGATGAAACTCTCATAG-3′ 5′-GGACCTTACGAATGTTGGCAA-3′
Human-TPI1 5′-CTCATCGGCACTCTGAACG-3′ 5′-GCGAAGTCGATATAGGCAGTAGG-3′
Human-GAPDH 5′-GGAGCGAGATCCCTCCAAAAT-3′ 5′- GGCTGTTGTCATACTTCTCATGG-3′
Human-PGAM 5′-TCTGGAGGCGCTCCTATGAT-3′ 5′-TCTGTGAGGTCTGCATACCTG-3′
Human-ENO1 5′-GCCGTGAACGAGAAGTCCTG-3′ 5′-ACGCCTGAAGAGACTCGGT-3′
Human-PKM2 5′-ATGTCGAAGCCCCATAGTGAA-3′ 5′-TGGGTGGTGAATCAATGTCCA-3′
Mouse-Nlrp3 5′-TGTGAGAAGCAGGTTCTACTCT-3′ 5′-TGTAGCGACTGTTGAGGTCCA-3′
Mouse-caspase-1 5′-AATACAACCACTCGTACACGTC-3′ 5′-AGCTCCAACCCTCGGAGAAA-3′
Mouse-Gsdmd 5′-TTCCAGTGCCTCCATGAATGT-3′ 5′-GCTGTGGACCTCAGTGATCT-3′
Mouse-Il-1β 5′-GAAATGCCACCTTTTGACAGTG-3′ 5′-TGGATGCTCTCATCAGGACAG-3′
Mouse-Pkm2 5′-CGCCTGGACATTGACTCTG-3′ 5′-GAAATTCAGCCGAGCCACATT-3′
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