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Updated: Aug 1, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Tumor Necrosis Factor Superfamily 14 (LIGHT) Restricts Neovascularization by Decreasing Circulating Endothelial
Chien-Yi Hsu1,2, Chun-Yao Huang1,2,3, Chun-Ming Shih1,2
1Taipei Heart Institute and Division of Cardiology, Department of Internal Medicine, Taipei Medical University, Taipei 110, Taiwan.
Abstract:
Tumor necrosis factor superfamily 14 (TNFSF14) is also known as the LT-related inducible ligand (LIGHT). It can bind to the herpesvirus invasion mediator and lymphotoxin-β receptor to perform its biological activity. LIGHT has multiple physiological functions, including strengthening the synthesis of nitric oxide, reactive oxygen species, and cytokines. LIGHT also stimulates angiogenesis in tumors and induces the synthesis of high endothelial venules; degrades the extracellular matrix in thoracic aortic dissection, and induces the expression of interleukin-8, cyclooxygenase-2, and cell adhesion molecules in endothelial cells. While LIGHT induces tissue inflammation, its effects on angiogenesis after tissue ischemia are unclear. Thus, we analyzed these effects in the current study. In this study, the animal model of hind limb ischemia surgery in C57BL/6 mice was performed. Doppler ultrasound, immunohistochemical staining, and Western blotting were employed to analyze the situation of angiogenesis. In addition, human endothelial progenitor cells (EPCs) were used for in vitro studies to analyze the possible mechanisms. The results in the animal study showed that LIGHT injection inhibited angiogenesis in ischemic limbs. For the in vitro studies, LIGHT inhibited the expression of integrins and E-selectin; decreased migration and tube formation capabilities, mitochondrial respiration, and succinate dehydrogenase activity; and promoted senescence in EPCs. Western blotting revealed that the impairment of EPC function by LIGHT may be due to its effects on the proper functioning of the intracellular Akt signaling pathway, endothelial nitrite oxide synthase (eNOS), and mitochondrial respiration. In conclusion, LIGHT inhibits angiogenesis after tissue ischemia. This may be related to the clamped EPC function.
Insights
Tumor necrosis factor superfamily 14 (LIGHT) inhibits angiogenesis in ischemic tissues. This protein impairs endothelial progenitor cell function, hindering blood vessel formation after injury.
Area of Science:
- Biochemistry
- Molecular Biology
- Immunology
Background:
- Tumor necrosis factor superfamily 14 (TNFSF14), also known as LIGHT, has diverse physiological roles.
- LIGHT's impact on angiogenesis following tissue ischemia remains largely uncharacterized.
- Understanding LIGHT's function in ischemia is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the role of LIGHT in angiogenesis after tissue ischemia.
- To elucidate the underlying mechanisms of LIGHT's effects on endothelial progenitor cells (EPCs).
Main Methods:
- Hind limb ischemia model in C57BL/6 mice.
- Doppler ultrasound, immunohistochemistry, and Western blotting for angiogenesis analysis.
- In vitro studies using human EPCs to assess cellular functions and signaling pathways.
Main Results:
- LIGHT injection significantly inhibited angiogenesis in ischemic limbs in vivo.
- In vitro, LIGHT reduced EPC migration, tube formation, mitochondrial respiration, and promoted senescence.
- LIGHT negatively impacted the Akt signaling pathway, eNOS, and mitochondrial respiration in EPCs.
Conclusions:
- LIGHT demonstrably inhibits angiogenesis in the context of tissue ischemia.
- Impaired EPC function, mediated by LIGHT, is a key factor in this inhibition.
- LIGHT may represent a therapeutic target for managing ischemic conditions.
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