Title Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence
Authors Jia, Yan
Kang, Xin
Tan, Lishan
Ren, Yifei
Qu, Lei
Tang, Jiawei
Liu, Gang
Wang, Suxia
Xiong, Zuying
Yang, Li
Affiliation Peking Univ, Shenzhen Hosp, Shenzhen Peking Univ Hong Kong Univ Sci & Technol, Dept Nephrol, Shenzhen, Peoples R China
Peking Univ First Hosp, Minist Hlth China, Inst Nephrol, Key Lab Renal Dis,Renal Div,Dept Med, Beijing, Peoples R China
Peking Univ First Hosp, Pathol Ctr, Lab Electron Microscopy, Beijing, Peoples R China
Issue Date 23-Mar-2021
Publisher FRONTIERS IN PHYSIOLOGY
Abstract Acute kidney injury (AKI) is a worldwide health problem currently lacking therapeutics that directly promote renal repair or prevent the occurrence of chronic fibrosis. DNA damage is a feature of many forms of kidney injury, and targeting DNA damage and repair might be effective strategies for kidney protection in AKI. Boosting nicotinamide adenine dinucleotide (NAD(+)) levels is thought to have beneficial effects on DNA damage repair and fibrosis in other organs. However, no kidney-related studies of such effects have been performed to date. Here, we have shown that NMN (an NAD(+) precursor) administration could significantly reduce tubular cell DNA damage and subsequent cellular senescence induced by hydrogen peroxide and hypoxia in human proximal tubular cells (HK-2 cells). The DNA damage inhibition, antiaging and anti-inflammatory effects of NMN were further confirmed in a unilateral ischemia-reperfusion injury (uIRI) mouse model. Most importantly, the antifibrosis activity of NMN was also shown in ischemic AKI mouse models, regardless of whether NMN was administered in advance or during the recovery phase. Collectively, these results suggest that NMN could significantly inhibit tubular cell DNA damage, senescence and inflammation. NMN administration might be an effective strategy for preventing or treating kidney fibrosis after AKI.
URI http://hdl.handle.net/20.500.11897/611505
ISSN 1664-042X
DOI 10.3389/fphys.2021.649547
Indexed SCI(E)
Appears in Collections: 深圳医院
第一医院

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