Nicotinamide protects against diabetic kidney disease through regulation of Sirt1

被引：1
|
作者：
Yang, Yeping [1 ]
Huang, Jinya [1 ]
Xie, Lijie [1 ]
Wang, Yilin [1 ]
Guo, Shizhe [1 ]
Wang, Meng [1 ]
Shao, Xiaoqing [1 ]
Liu, Wenjuan [1 ]
Wang, Yi [1 ]
Li, Qin [2 ]
Wu, Xia [3 ]
Zhang, Zhaoyun [1 ,4 ]
Zeng, Fangfang [1 ]
Gong, Wei [1 ]
机构：
[1] Fudan Univ, Huashan Hosp, Div Endocrinol & Metab, Shanghai 200040, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Div Endocrinol & Metab, Sch Med, Shanghai 200011, Peoples R China
[3] Jingan Dist Ctr Hosp Shanghai, Dept Endocrinol & Metab, Shanghai 200040, Peoples R China
[4] Fudan Univ, Inst Endocrinol & Diabetol, Shanghai 200040, Peoples R China
来源：
ENDOCRINE | 2024年 / 85卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Nicotinamide; Diabetic kidney disease; Proximal tubule; Fibrosis; Oxidative stress; Sirtuin; 1; OXIDATIVE STRESS; SKELETAL-MUSCLE; CELL-SURVIVAL; TGF-BETA; METABOLISM; FIBROSIS; INJURY; OVEREXPRESSION; PATHWAY;
D O I：
10.1007/s12020-024-03721-7
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
PurposeTo investigate the effect of nicotinamide (Nam) on diabetic kidney disease (DKD) in mice and explore its mechanism.MethodsThirty DBA/2 J mice were randomly assigned to three groups. After 8 weeks of hyperglycemia induced by streptozocin (STZ), Nam and saline were administrated to STZ + Nam and STZ + NS mice, respectively, for 8 weeks. Non-diabetic mice (NDM) were used as control group. Twenty In2-/- Akita mice were randomly divided into two groups. After 8 weeks of hyperglycemia, Nam and saline were administered to Akita + Nam and Akita + NS mice, respectively, for 6 weeks. Wild-type littermates were used as control group. Markers of renal injury were analyzed, and the molecular mechanisms were explored in human proximal tubular HK2 cells.ResultsUrinary albumin-to-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1) decreased in the STZ + Nam and Akita + Nam groups. Pathological analysis showed that Nam improved the structure of glomerular basement membrane, ameliorated glomerular sclerosis, and decreased the accumulation of extracellular matrix and collagen. Compared to the diabetic control group, renal fibrosis, inflammation, and oxidative stress were reduced in the Nam-treated mice. The expression of sirtuin 1 (Sirt1) in human proximal tubular HK2 cells was inhibited by high glucose and Nam treatment enhanced its expression. However, in HK2 cells with Sirt1 knockdown, the protective effect of Nam was abolished, indicating that the beneficial effect of Nam was partially dependent on Sirt1.ConclusionsNam has a renoprotective effect against renal injury caused by hyperglycemia and may be a potential target for the treatment of DKD.
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收藏
页码：99 / 121
页数：23
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