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Endogenous Nampt upregulation is associated with diabetic nephropathy
inflammatory-fibrosis through the NF-?B p65 and Sirt1 pathway; NMN alleviates
diabetic nephropathy inflammatory-fibrosis by inhibiting endogenous Nampt
#MMPMID29104634
Chen Y
; Liang Y
; Hu T
; Wei R
; Cai C
; Wang P
; Wang L
; Qiao W
; Feng L
Exp Ther Med
2017[Nov]; 14
(5
): 4181-4193
PMID29104634
show ga
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)-?B 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-?B 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-?B 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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