Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory‑fibrosis through the NF‑κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory‑fibrosis by inhibiting endogenous Nampt

Chen,Ye; Liang,Yuzhen; Hu,Tingting; Wei,Riming; Cai,Congjie; Wang,Ping; Wang,Lingyu; Qiao,Wei; Feng,Leping

doi:10.3892/etm.2017.5098

Endogenous Nampt upregulation is associated with diabetic nephropathy inflammatory‑fibrosis through the NF‑κB p65 and Sirt1 pathway; NMN alleviates diabetic nephropathy inflammatory‑fibrosis by inhibiting endogenous Nampt

Authors:
- Ye Chen
- Yuzhen Liang
- Tingting Hu
- Riming Wei
- Congjie Cai
- Ping Wang
- Lingyu Wang
- Wei Qiao
- Leping Feng
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Affiliations: Department of Nutrition and Health, Public Health School, Guilin Medical University, Guilin, Guangxi 541004, P.R. China, Endocrinology Department, Diabetic Metabolic Center, First Affiliated Clinical Hospital, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Scientific Experiment Center, Biotechnology School, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
Published online on: September 1, 2017 https://doi.org/10.3892/etm.2017.5098
Pages: 4181-4193
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro‑fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)‑κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro‑inflammatory and pro‑fibrotic cytokines in vivo and in vitro, is reported. The present results demonstrate that the expression of vimentin and fibronectin was directly implicated in endogenous Nampt upregulation. The expression levels of Poly(ADP‑ribose) polymerase‑1, NF‑κB p65, forkhead box protein O1 and B‑cell lymphoma 2‑like protein 4 were also significantly increased at 96 h compared with control group (P<0.01) respectively in response to endogenous Nampt upregulation. Furthermore, the expression level of Sirt1 was significantly reduced (P<0.05), and the NAD and NADH levels, and the NAD/NADH ratio are significantly altered in STZ‑induced diabetic rats (P<0.01). Treatment with FK866 and nicotinamide mononucleotide (NMN) led to downregulation of vimentin and fibronectin, respectively. These results suggest a novel role of Nampt as a pro‑inflammatory cytokine of mesangial fibrotic signaling. The Nampt‑NF‑κB p65 and Sirt1 signaling pathway serves a pivotal role in affecting the expression of fibrosis factors in diabetic nephropathy (DN) glomerular fibrosis processing. It is also suggested that prevention of endogenous Nampt upregulation may be critical in the treatment of DN pro‑inflammatory fibrosis and NMN is likely to be a potential pharmacological agent for the treatment of resistant DN nephritic fibrosis.

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