Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis

Dandan Sun; Kun Guo; Naixin Liu; Yilin Li; Yuansheng Li; Yan Hu; Shanshan Li; Zhe Fu; Yinglei Wang; Yutong Wu; Yingxuan Zhang; Jiayi Li; Chao Li; Zhuo Wang; Zijian Kang; Jun Sun; Ying Wang; Xinwang Yang

doi:10.1093/burnst/tkad035

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Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis

更新时间：2024-02-04

- Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis
- Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis
- Burns & Trauma 2023年11卷第1期
- 作者机构：
  
  1. Department of Anatomy and Histology and & Embryology
  2. Kunming Medical University
  3. Department of Biochemistry and Molecular Biology
  4. Key Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes
- 作者简介：
- 基金信息：
  
  This work was supported by grants from the National Natural Science Foundation of China (32360138, 32060212, 32301054 and 81760648), Key Program of Yunnan Fundamental Research Project (202301AS070036), Outstanding Youth Program of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation (202301AY070001-301), Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation (202101AY070001-006 and 202101AY070001-036).
- DOI：10.1093/burnst/tkad035
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-11-15，
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Dandan Sun, Kun Guo, Naixin Liu, 等. Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis[J]. Burns & Trauma, 2023,11(1).

Dandan Sun, Kun Guo, Naixin Liu, Yilin Li, Yuansheng Li, Yan Hu, Shanshan Li, Zhe Fu, Yinglei Wang, Yutong Wu, Yingxuan Zhang, Jiayi Li, Chao Li, Zhuo Wang, Zijian Kang, Jun Sun, Ying Wang, Xinwang Yang, Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis, Burns & Trauma, Volume 11, 2023, tkad035, https://doi.org/10.1093/burnst/tkad035
Dandan Sun, Kun Guo, Naixin Liu, 等. Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis[J]. Burns & Trauma, 2023,11(1). DOI： 10.1093/burnst/tkad035.

Dandan Sun, Kun Guo, Naixin Liu, Yilin Li, Yuansheng Li, Yan Hu, Shanshan Li, Zhe Fu, Yinglei Wang, Yutong Wu, Yingxuan Zhang, Jiayi Li, Chao Li, Zhuo Wang, Zijian Kang, Jun Sun, Ying Wang, Xinwang Yang, Peptide RL-QN15 promotes wound healing of diabetic foot ulcers through p38 mitogen-activated protein kinase and smad3/miR-4482-3p/vascular endothelial growth factor B axis, Burns & Trauma, Volume 11, 2023, tkad035, https://doi.org/10.1093/burnst/tkad035 DOI：

摘要

Abstract

BackgroundWound management of diabetic foot ulcers (DFUs) is a complex and challenging task

and existing strategies fail to meet clinical needs. Therefore

it is important to develop novel drug candidates and discover new therapeutic targets. However

reports on peptides as molecular probes for resolving issues related to DFUs remain rare. This study utilized peptide RL-QN15 as an exogenous molecular probe to investigate the underlying mechanism of endogenous non-coding RNA in DFU wound healing. The aim was to generate novel insights for the clinical management of DFUs and identify potential drug targets.MethodsWe investigated the wound-healing efficiency of peptide RL-QN15 under diabetic conditions using in vitro and in vivo experimental models. RNA sequencing

in vitro transfection

quantitative real-time polymerase chain reaction

western blotting

dual luciferase reporter gene detection

in vitro cell scratches

and cell proliferation and migration assays were performed to explore the potential mechanism underlying the promoting effects of RL-QN15 on DFU repair.ResultsPeptide RL-QN15 enhanced the migration and proliferation of human immortalized keratinocytes (HaCaT cells) in a high-glucose environment and accelerated wound healing in a DFU rat model. Based on results from RNA sequencing

we defined a new microRNA (miR-4482-3p) related to the promotion of wound healing. The bioactivity of miR-4482-3p was verified by inhibiting and overexpressing miR-4482-3p. Inhibition of miR-4482-3p enhanced the migration and proliferation ability of HaCaT cells as well as the expression of vascular endothelial growth factor B (VEGFB). RL-QN15 also promoted the migration and proliferation ability of HaCaT cells

and VEGFB expression was mediated via inhibition of miR-4482-3p expression by the p38 mitogen-activated protein kinase (p38MAPK) and smad3 signaling pathways.ConclusionsRL-QN15 is an effective molecule for the treatment of DFUs

with the underlying mechanism related to the inhibition of miR-4482-3p expression via the p38MAPK and smad3 signaling pathways

ultimately promoting re-epithelialization

angiogenesis and wound healing. This study provides a theoretical basis for the clinical application of RL-QN15 as a molecular probe in promoting DFU wound healing.

关键词

Keywords

RL-QN15Diabetic foot ulcerWound healingmiR-4482-3pVascular endothelial growth factor BPeptideMitogen-activated protein kinase

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