{"doi":"10.1016/j.jbc.2023.105027","title":"Nicotinamide N-methyltransferase mediates lipofibroblast–myofibroblast transition and apoptosis resistance","abstract":"Metabolism controls cellular phenotype and fate. In this report, we demonstrate that nicotinamide N-methyltransferase (NNMT), a metabolic enzyme that regulates developmental stem cell transitions and tumor progression, is highly expressed in human idiopathic pulmonary fibrosis (IPF) lungs, and is induced by the pro-fibrotic cytokine, transforming growth factor-β1 (TGF-β1) in lung fibroblasts. NNMT silencing reduces the expression of extracellular matrix proteins, both constitutively and in response to TGF-β1. Furthermore, NNMT controls the phenotypic transition from homeostatic, pro-regenerative lipofibroblasts to pro-fibrotic myofibroblasts. This effect of NNMT is mediated, in part, by the downregulation of lipogenic transcription factors, TCF21 and PPARγ, and the induction of a less proliferative but more differentiated myofibroblast phenotype. NNMT confers an apoptosis-resistant phenotype to myofibroblasts that is associated with the downregulation of pro-apoptotic members of the Bcl-2 family, including Bim and PUMA. Together, these studies indicate a critical role for NNMT in the metabolic reprogramming of fibroblasts to a pro-fibrotic and apoptosis-resistant phenotype and support the concept that targeting this enzyme may promote regenerative responses in chronic fibrotic disorders such as IPF.","journal":"Journal of Biological Chemistry","year":2023,"id":339938,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9605,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":650940,"name":"B. Deskin","orcid":"0000-0001-7850-5146","position":1,"is_corresponding":false},{"id":492007,"name":"Ashish Kurundkar","orcid":"0000-0001-9078-1039","position":2,"is_corresponding":false},{"id":456544,"name":"Santosh Yadav","orcid":"0000-0003-1920-3919","position":3,"is_corresponding":false},{"id":1073939,"name":"Yasuka Matsunaga","orcid":"0000-0003-2154-1642","position":4,"is_corresponding":false},{"id":1074296,"name":"Justin Manges","orcid":null,"position":5,"is_corresponding":false},{"id":1074297,"name":"Nia Smith","orcid":null,"position":6,"is_corresponding":false},{"id":667240,"name":"K.G. Dsouza","orcid":null,"position":7,"is_corresponding":false},{"id":376497,"name":"Matthew E. Burow","orcid":"0000-0002-0642-6630","position":8,"is_corresponding":false},{"id":228870,"name":"Victor J. Thannickal","orcid":"0000-0003-4266-8677","position":9,"is_corresponding":false},{"id":814068,"name":"Mohammad Rehan","orcid":"0000-0003-3943-2807","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:10:49.535464Z","pmid":"37423298","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}