Wang Zhen-Hua, Bao Xiao-Gang, Hu Jun-Jie, Shen Si-Bo, Xu Guo-Hua, Wu Ye-Lin
Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai, China.
Front Pharmacol. 2021 May 12;12:671563. doi: 10.3389/fphar.2021.671563. eCollection 2021.
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. mice that were treated with NR-supplemented food (400 mg/kg/d) for 12 weeks exhibited higher wound healing rates and angiogenesis than untreated mice. In agreement with this phenotype, NR supplementation significantly increased the number of blood EPCs and bone marrow (BM)-derived EPCs of 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 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.
血管生成不足与糖尿病（DM）患者伤口愈合困难直接相关。富集内皮祖细胞（EPC）是治疗糖尿病伤口的一种有前景但具有挑战性的方法。在此，我们研究烟酰胺核糖（NR）对EPC功能的作用，以改善糖尿病伤口的愈合。用补充NR的食物（400mg/kg/d）治疗12周的小鼠比未治疗的小鼠表现出更高的伤口愈合率和血管生成。与这种表型一致，补充NR显著增加了小鼠血液EPC和骨髓（BM）来源的EPC数量，以及BM-EPC的管形成和黏附功能。此外，与从未治疗小鼠分离的BM-EPC相比，补充NR的BM-EPC显示出更高的沉默调节蛋白1（Sirt1）、磷酸化的腺苷单磷酸激活蛋白激酶（p-AMPK）表达，以及更低的乙酰化过氧化物酶体增殖物激活受体γ共激活因子（PGC-1α）表达。BM-EPC中Sirt1的敲低显著消除了NR的管形成和黏附功能以及p-AMPK和去乙酰化PGC-1α的表达。AMPK的抑制消除了NR调节的EPC功能，但对Sirt1表达没有影响，表明NR通过Sirt1-AMPK途径增强EPC功能。总体而言，本研究表明口服NR可增强EPC功能以促进糖尿病伤口愈合，表明补充NR可能是预防糖尿病并发症进展的一种有前景的策略。
