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Cellular metabolism-related epigenetic modulation plays a pivotal role in the maintenance of cellular homeostasis. Nicotinamide N-methyltransferase (NNMT) serves as a crucial link between cellular metabolism and epigenetics by catalyzing nicotinamide methylation using the universal methyl donor S-adenosyl-L-methionine. This direct connection bridges the methylation-mediated one-carbon metabolism with nicotinamide adenine dinucleotide levels. Numerous studies have revealed tissue-specific differences in NNMT expression and activity, indicating that its varied physiological and pathological roles depend on its distribution. In this review, we provide an overview of the NNMT involvement in various pathological conditions, including cancer, liver disease, obesity, diabetes, brain disease, pulmonary disease, cardiovascular disease, and kidney disease. By synthesizing this information, our article aims to enhance our understanding of the cellular mechanisms underlying NNMT biology related to diverse diseases and lay the molecular groundwork for developing therapeutic strategies for pharmacological interventions.
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http://dx.doi.org/10.1007/s12272-024-01519-9 | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
JCI Insight
September 2025
Edinburgh Medical School: Biomedical Sciences & Euan MacDonald Centre for M, University of Edinburgh, Edinburgh, United Kingdom.
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated SMA patients, indicative of alterations in brain development.
View Article and Find Full Text PDFClin J Am Soc Nephrol
September 2025
University College London Great Ormond Street Hospital for Children and Institute of Child Health, London, UK.
Background: Experience with icodextrin use in children on long-term peritoneal dialysis is limited. We describe international icodextrin prescription practices and their impact on clinical outcomes: ultrafiltration, blood pressure control, residual kidney function (RKF), technique and patient survival.
Methods: We included patients under 21 years enrolled in the International Pediatric Peritoneal Dialysis Network (IPPN) between 2007 and 2024, on automated PD with a daytime dwell.
Clin J Am Soc Nephrol
September 2025
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland USA.
Socioeconomic, environmental and lifestyle factors shape kidney health. Among the social determinants of health, access to healthy foods is particularly significant. As a basic need, food is integral to an individual's identity, culture, and health.
View Article and Find Full Text PDFClin J Am Soc Nephrol
September 2025
Kidney Division, Peking University First Hospital, Peking University Institute of Nephrology; Key Laboratory of Kidney Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China.
Background: The Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) trial demonstrated that glucocorticoid therapy reduced proteinuria and improved kidney outcomes in patients with Immunoglobulin A Nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) plays a central role in IgAN pathogenesis by promoting immune complex formation. However, the effects of glucocorticoid on pathogenic IgA levels remain unclear.
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