LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases
PurposeTo study the angiogenic capacity of antimicrobial peptide LL37 (cathelicidin antimicrobial peptide), explore its molecular mechanisms, and provide new ideas for treating lower limb ischemic diseases.MethodsLL37 was applied exogenously to human umbilical vein endothelial cells (HUVECs), and it...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1587351/full |
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| author | Yingying Yang Gang Wu Yini Wang Qiancheng Mao Dongxu Zhang Jitao Wu |
| author_facet | Yingying Yang Gang Wu Yini Wang Qiancheng Mao Dongxu Zhang Jitao Wu |
| author_sort | Yingying Yang |
| collection | DOAJ |
| description | PurposeTo study the angiogenic capacity of antimicrobial peptide LL37 (cathelicidin antimicrobial peptide), explore its molecular mechanisms, and provide new ideas for treating lower limb ischemic diseases.MethodsLL37 was applied exogenously to human umbilical vein endothelial cells (HUVECs), and its effects on cell proliferation, migration, and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8), plate cloning, scratch, and angiogenesis assays. A mouse lower limb ischemia model was established, with LL37 injected intramuscularly on days 0, 4, and 8. Blood flow recovery was evaluated by laser Doppler flowmetry. Immunofluorescence staining detected cluster of differentiation 31 (CD31) and cluster of differentiation 34 (CD34) expression, while Hematoxylin and Eosin (H&E) staining assessed muscle cell morphology. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyzed gene and protein expression changes in HUVECs.ResultsLL37 enhanced the proliferative, migratory, and pro-angiogenic abilities of HUVECs. It significantly improved blood flow recovery in ischemic limbs, with higher CD31/CD34 expression and more intact muscle morphology. qRT-PCR analysis demonstrated elevated expression of angiogenesis-related genes in LL37-treated HUVECs. Western blotting revealed increased vascular endothelial growth factor A (VEGFA) expression and enhanced phosphorylation levels of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in LL37-treated cells.ConclusionLL37 promotes angiogenesis via the VEGFA-PI3K/AKT/mTOR pathway, showing potential for treating lower limb ischemia by improving perfusion. |
| format | Article |
| id | doaj-art-8d9a3c4420b74807a9dba7ff882fc48b |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-8d9a3c4420b74807a9dba7ff882fc48b2025-08-20T03:14:47ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15873511587351LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseasesYingying YangGang WuYini WangQiancheng MaoDongxu ZhangJitao WuPurposeTo study the angiogenic capacity of antimicrobial peptide LL37 (cathelicidin antimicrobial peptide), explore its molecular mechanisms, and provide new ideas for treating lower limb ischemic diseases.MethodsLL37 was applied exogenously to human umbilical vein endothelial cells (HUVECs), and its effects on cell proliferation, migration, and angiogenesis were assessed using Cell Counting Kit-8 (CCK-8), plate cloning, scratch, and angiogenesis assays. A mouse lower limb ischemia model was established, with LL37 injected intramuscularly on days 0, 4, and 8. Blood flow recovery was evaluated by laser Doppler flowmetry. Immunofluorescence staining detected cluster of differentiation 31 (CD31) and cluster of differentiation 34 (CD34) expression, while Hematoxylin and Eosin (H&E) staining assessed muscle cell morphology. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyzed gene and protein expression changes in HUVECs.ResultsLL37 enhanced the proliferative, migratory, and pro-angiogenic abilities of HUVECs. It significantly improved blood flow recovery in ischemic limbs, with higher CD31/CD34 expression and more intact muscle morphology. qRT-PCR analysis demonstrated elevated expression of angiogenesis-related genes in LL37-treated HUVECs. Western blotting revealed increased vascular endothelial growth factor A (VEGFA) expression and enhanced phosphorylation levels of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in LL37-treated cells.ConclusionLL37 promotes angiogenesis via the VEGFA-PI3K/AKT/mTOR pathway, showing potential for treating lower limb ischemia by improving perfusion.https://www.frontiersin.org/articles/10.3389/fphar.2025.1587351/fullantimicrobial peptideLL37VEGFA-PI3K/AKT/mTOR pathwayangiogenesislower limb ischemia |
| spellingShingle | Yingying Yang Gang Wu Yini Wang Qiancheng Mao Dongxu Zhang Jitao Wu LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases Frontiers in Pharmacology antimicrobial peptide LL37 VEGFA-PI3K/AKT/mTOR pathway angiogenesis lower limb ischemia |
| title | LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases |
| title_full | LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases |
| title_fullStr | LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases |
| title_full_unstemmed | LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases |
| title_short | LL37 promotes angiogenesis: a potential therapeutic strategy for lower limb ischemic diseases |
| title_sort | ll37 promotes angiogenesis a potential therapeutic strategy for lower limb ischemic diseases |
| topic | antimicrobial peptide LL37 VEGFA-PI3K/AKT/mTOR pathway angiogenesis lower limb ischemia |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1587351/full |
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