Journal
FRONTIERS IN PHARMACOLOGY
Volume 12, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.671563
Keywords
diabetes mellitus; endothelial precursor cells; nicotinamide riboside; wound healing; sirtuin 1; adenosine monophosphate-activated protein kinase
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Funding
- National Natural Science Foundation of China [81772363, 51802221]
- Shanghai Sailing Program [21YF1458200]
- Youth Initial funding of Naval Medical University [2018QN13]
- Special Fund of Changzheng Hospital [2019CZJS104]
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Oral uptake of nicotinamide riboside enhances EPC function to promote diabetic wound healing, indicating a promising strategy to prevent the progression of diabetic complications.
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 gamma coactivator (PGC-1 alpha) 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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