ArticleKidney diseases (Basel, Switzerland)2021
Nicotinamide Supplementation Attenuates Renal Interstitial Fibrosis via Boosting the Activity of Sirtuins.
Article in Kidney diseases (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- A review of the sirtuins family: pivotal regulators and emerging therapeutic targets in renal fibrosis.Renal failure · 2026Review
- NADBiochemistry and biophysics reports · 2026Article
- The Pof1 nicotinamide mononucleotide adenylyl transferase has a non-canonical role in NADThe Journal of biological chemistry · 2026Article
- Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nicotinamide Attenuates Complement and Coagulation Pathways and Resultant Renal Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- NADTrends in molecular medicine · 2025Review
- The role of NADnpj metabolic health and disease · 2025Review
- Bioinformatics analysis of comorbid mechanisms between ischemic stroke and end stage renal disease.Scientific reports · 2025Article
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- Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury.CNS neuroscience & therapeutics · 2024Article
- NAD metabolism: Role in senescence regulation and aging.Aging cell · 2024Review
- Article
- Astaxanthin attenuates cognitive deficits in Alzheimer's disease models by reducing oxidative stress via the SIRT1/PGC-1α signaling pathway.Cell & bioscience · 2023Article
- The Histone Deacetylases Hst1 and Rpd3 Integrate De Novo NADInternational journal of molecular sciences · 2023Article
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- Roles of NADInternational journal of molecular sciences · 2022Review
- NADCells · 2022Review
- Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide).iScience · 2022Article
- The significance of NAD + metabolites and nicotinamide N-methyltransferase in chronic kidney disease.Scientific reports · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundProgressive tubulointerstitial fibrosis (TIF) is the final common pathway leading to ESRD. There is an urgent need to develop effective approaches slowing the progression of TIF. Previous studies showed that systemic supplementation of nicotinamide (NAM) increases renal NAD
methodsIn vivo, we injected NAM (0.25 mg/g) 3 days before unilateral ureter obstruction (UUO) till day 7 post-operation. In vitro, mouse primary proximal tubular epithelial cells (PTCs), rat renal NRK-49F cells, and human renal proximal tubular epithelial cell (HK-2) were pretreated with the indicated concentration of NAM 1 h before incubation with transform growth factor-β1 (TGF-β1) or aristolochic acid (AA) for 24 or 48 h. To evaluate the role of sirtuins (SIRTs), PTCs were pretreated with EX527 or resveratrol 30 min before incubation with NAM and TGF-β1.
resultsIn the present study, we demonstrated that NAM supplementation prevented UUO-induced TIF, and AA-induced renal injury. NAM also decreased the expression of pro-fibrotic proteins and pro-inflammatory cytokines (IL-6 and TNF-α) and attenuated interstitial inflammation. In vitro experiment showed that, NAM inhibited AA-induced G2/M arrest of HK-2 cells by downregulating the expression of cyclin G1, a target gene of p53. In addition, NAM inhibited TGF-β1-induced fibroblast proliferation and activation shown as downregulated expression of collagen I, fibronectin, PCNA, cyclin D1, IL-6, and TNF-α. NAM decreased the acetylation of Smad3 and p53. EX527, an inhibitor of SIRT1, reversed the effect of NAM on TGF-β1-induced matrix protein production. However, resveratrol, a SIRT1 activator, did not further boost the protective effect of NAM on reducing matrix protein production.
conclusionsTaken together, these data indicate that NAM supplementation could inhibit TIF at least partially by boosting the activity of sirtuins.
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