Cargando…

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

BACKGROUND: Wound 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 r...

Descripción completa

Detalles Bibliográficos
Autores principales: Sun, Dandan, Guo, Kun, Liu, Naixin, Li, Yilin, Li, Yuansheng, Hu, Yan, Li, Shanshan, Fu, Zhe, Wang, Yinglei, Wu, Yutong, Zhang, Yingxuan, Li, Jiayi, Li, Chao, Wang, Zhuo, Kang, Zijian, Sun, Jun, Wang, Ying, Yang, Xinwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654477/
https://www.ncbi.nlm.nih.gov/pubmed/38026443
http://dx.doi.org/10.1093/burnst/tkad035
_version_ 1785147849047015424
author Sun, Dandan
Guo, Kun
Liu, Naixin
Li, Yilin
Li, Yuansheng
Hu, Yan
Li, Shanshan
Fu, Zhe
Wang, Yinglei
Wu, Yutong
Zhang, Yingxuan
Li, Jiayi
Li, Chao
Wang, Zhuo
Kang, Zijian
Sun, Jun
Wang, Ying
Yang, Xinwang
author_facet Sun, Dandan
Guo, Kun
Liu, Naixin
Li, Yilin
Li, Yuansheng
Hu, Yan
Li, Shanshan
Fu, Zhe
Wang, Yinglei
Wu, Yutong
Zhang, Yingxuan
Li, Jiayi
Li, Chao
Wang, Zhuo
Kang, Zijian
Sun, Jun
Wang, Ying
Yang, Xinwang
author_sort Sun, Dandan
collection PubMed
description BACKGROUND: Wound 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. METHODS: We 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. RESULTS: Peptide 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. CONCLUSIONS: RL-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.
format Online
Article
Text
id pubmed-10654477
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-106544772023-11-15 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 Sun, Dandan Guo, Kun Liu, Naixin Li, Yilin Li, Yuansheng Hu, Yan Li, Shanshan Fu, Zhe Wang, Yinglei Wu, Yutong Zhang, Yingxuan Li, Jiayi Li, Chao Wang, Zhuo Kang, Zijian Sun, Jun Wang, Ying Yang, Xinwang Burns Trauma Research Article BACKGROUND: Wound 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. METHODS: We 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. RESULTS: Peptide 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. CONCLUSIONS: RL-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. Oxford University Press 2023-11-15 /pmc/articles/PMC10654477/ /pubmed/38026443 http://dx.doi.org/10.1093/burnst/tkad035 Text en © The Author(s) 2023. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Sun, Dandan
Guo, Kun
Liu, Naixin
Li, Yilin
Li, Yuansheng
Hu, Yan
Li, Shanshan
Fu, Zhe
Wang, Yinglei
Wu, Yutong
Zhang, Yingxuan
Li, Jiayi
Li, Chao
Wang, Zhuo
Kang, Zijian
Sun, Jun
Wang, Ying
Yang, Xinwang
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654477/
https://www.ncbi.nlm.nih.gov/pubmed/38026443
http://dx.doi.org/10.1093/burnst/tkad035
work_keys_str_mv AT sundandan peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT guokun peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT liunaixin peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT liyilin peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT liyuansheng peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT huyan peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT lishanshan peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT fuzhe peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT wangyinglei peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT wuyutong peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT zhangyingxuan peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT lijiayi peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT lichao peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT wangzhuo peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT kangzijian peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT sunjun peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT wangying peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis
AT yangxinwang peptiderlqn15promoteswoundhealingofdiabeticfootulcersthroughp38mitogenactivatedproteinkinaseandsmad3mir44823pvascularendothelialgrowthfactorbaxis