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Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway

Lack of vascularization is directly associated with refractory wound healing in diabetes mellitus (DM). Enrichment of endothelial precursor cells (EPCs) is a promising but challenging approach for the treatment of diabetic wounds. Herein, we investigate the action of nicotinamide riboside (NR) on EP...

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Autores principales: Wang, Zhen-hua, Bao, Xiao-gang, Hu, Jun-jie, Shen, Si-bo, Xu, Guo-hua, Wu, Ye-lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149616/
https://www.ncbi.nlm.nih.gov/pubmed/34054544
http://dx.doi.org/10.3389/fphar.2021.671563
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author Wang, Zhen-hua
Bao, Xiao-gang
Hu, Jun-jie
Shen, Si-bo
Xu, Guo-hua
Wu, Ye-lin
author_facet Wang, Zhen-hua
Bao, Xiao-gang
Hu, Jun-jie
Shen, Si-bo
Xu, Guo-hua
Wu, Ye-lin
author_sort Wang, Zhen-hua
collection PubMed
description Lack of vascularization is directly associated with refractory wound healing in diabetes mellitus (DM). Enrichment of endothelial precursor cells (EPCs) is a promising but challenging approach for the treatment of diabetic wounds. Herein, we investigate the action of nicotinamide riboside (NR) on EPC function for improved healing of diabetic wounds. Db/db mice that were treated with NR-supplemented food (400 mg/kg/d) for 12 weeks exhibited higher wound healing rates and angiogenesis than untreated db/db mice. In agreement with this phenotype, NR supplementation significantly increased the number of blood EPCs and bone marrow (BM)-derived EPCs of db/db mice, as well as the tube formation and adhesion functions of BM-EPCs. Furthermore, NR-supplemented BM-EPCs showed higher expression of sirtuin 1 (Sirt1), phosphorylated adenosine monophosphate–activated protein kinase (p-AMPK), and lower expression of acetylated peroxisome proliferator–activated receptor γ coactivator (PGC-1α) than BM-EPCs isolated from untreated db/db mice. Knockdown of Sirt1 in BM-EPCs significantly abolished the tube formation and adhesion function of NR as well as the expression of p-AMPK and deacetylated PGC-1a. Inhibition of AMPK abolished the NR-regulated EPC function but had no effect on Sirt1 expression, demonstrating that NR enhances EPC function through the Sirt1-AMPK pathway. Overall, this study demonstrates that the oral uptake of NR enhances the EPC function to promote diabetic wound healing, indicating that NR supplementation might be a promising strategy to prevent the progression of diabetic complications.
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spelling pubmed-81496162021-05-27 Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway Wang, Zhen-hua Bao, Xiao-gang Hu, Jun-jie Shen, Si-bo Xu, Guo-hua Wu, Ye-lin Front Pharmacol Pharmacology Lack of vascularization is directly associated with refractory wound healing in diabetes mellitus (DM). Enrichment of endothelial precursor cells (EPCs) is a promising but challenging approach for the treatment of diabetic wounds. Herein, we investigate the action of nicotinamide riboside (NR) on EPC function for improved healing of diabetic wounds. Db/db mice that were treated with NR-supplemented food (400 mg/kg/d) for 12 weeks exhibited higher wound healing rates and angiogenesis than untreated db/db mice. In agreement with this phenotype, NR supplementation significantly increased the number of blood EPCs and bone marrow (BM)-derived EPCs of db/db mice, as well as the tube formation and adhesion functions of BM-EPCs. Furthermore, NR-supplemented BM-EPCs showed higher expression of sirtuin 1 (Sirt1), phosphorylated adenosine monophosphate–activated protein kinase (p-AMPK), and lower expression of acetylated peroxisome proliferator–activated receptor γ coactivator (PGC-1α) than BM-EPCs isolated from untreated db/db mice. Knockdown of Sirt1 in BM-EPCs significantly abolished the tube formation and adhesion function of NR as well as the expression of p-AMPK and deacetylated PGC-1a. Inhibition of AMPK abolished the NR-regulated EPC function but had no effect on Sirt1 expression, demonstrating that NR enhances EPC function through the Sirt1-AMPK pathway. Overall, this study demonstrates that the oral uptake of NR enhances the EPC function to promote diabetic wound healing, indicating that NR supplementation might be a promising strategy to prevent the progression of diabetic complications. Frontiers Media S.A. 2021-05-12 /pmc/articles/PMC8149616/ /pubmed/34054544 http://dx.doi.org/10.3389/fphar.2021.671563 Text en Copyright © 2021 Wang, Bao, Hu, Shen, Xu and Wu. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Pharmacology
Wang, Zhen-hua
Bao, Xiao-gang
Hu, Jun-jie
Shen, Si-bo
Xu, Guo-hua
Wu, Ye-lin
Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway
title Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway
title_full Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway
title_fullStr Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway
title_full_unstemmed Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway
title_short Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway
title_sort nicotinamide riboside enhances endothelial precursor cell function to promote refractory wound healing through mediating the sirt1/ampk pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149616/
https://www.ncbi.nlm.nih.gov/pubmed/34054544
http://dx.doi.org/10.3389/fphar.2021.671563
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