94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1587351
This article is part of the Research TopicInnovative Approaches for Wound TreatmentView all 10 articles
LL37 Promotes Angiogenesis: A Potential Therapeutic Strategy for Lower Limb Ischemic Diseases
Provisionally accepted- Yantai Yuhuangding Hospital, Yantai, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Purpose: To 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.Methods: LL37 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.Results: LL37 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.LL37 promotes angiogenesis via the VEGFA-PI3K/AKT/mTOR pathway, showing potential for treating lower limb ischemia by improving perfusion.
Keywords: Antimicrobial peptide, LL37, VEGFA-PI3K/AKT/mTOR pathway, Angiogenesis, Lower limb ischemia
Received: 04 Mar 2025; Accepted: 08 Apr 2025.
Copyright: © 2025 Yang, WU, Wang, Mm, Zhang and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yingying Yang, Yantai Yuhuangding Hospital, Yantai, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.