Reprogramming lymphatic endothelial glucose metabolism for the treatment of lymphangiogenesis-related disease
Lymphangiogenesis plays important roles in the pathogenesis of several human diseases, including keratitis, transplant rejection, and cancers. Dysregulated glucose metabolism has emerged as a critical driver of pathological lymphangiogenesis. This study aimed to identify novel regulators of this pro...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
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| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S104366182500252X |
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| Summary: | Lymphangiogenesis plays important roles in the pathogenesis of several human diseases, including keratitis, transplant rejection, and cancers. Dysregulated glucose metabolism has emerged as a critical driver of pathological lymphangiogenesis. This study aimed to identify novel regulators of this process and elucidate their roles in the metabolic regulation of lymphatic endothelial cells (LECs). miR-484 was identified as a key regulator of LECs, with its expression down-regulated under inflammatory stress and in a suture-induced corneal lymphangiogenesis murine model. Overexpression of miR-484 inhibited the proliferation, migration, tube formation, and sprouting abilities of LECs and corneal lymphangiogenesis in vivo. Mechanistically, miR-484 directly targeted hexokinase 2 (HK2), a central enzyme in glycolysis, thereby modulating glucose metabolism and mitochondrial function to restrain lymphangiogenesis. Moreover, exosome-mediated delivery of miR-484 enhanced its anti-lymphangiogenic efficacy while exhibiting favorable biosafety. Collectively, these findings highlight the miR-484-HK2 axis as a potential therapeutic target and support the use of exosome-based strategies for safe and effective intervention in pathological lymphangiogenesis. |
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| ISSN: | 1096-1186 |