{"doi":"10.1016/j.jcmgh.2023.09.010","title":"Matrix Gla Protein, a New Target Fighting Against Fibrosis of Nonalcoholic Steatohepatitis?","abstract":"Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease linked to obesity and type 2 diabetes, affecting 30% of the global population.1Younossi Z.M. Koenig A.B. Abdelatif D. et al.Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes.Hepatology. 2016; 64: 73-84Crossref PubMed Scopus (6362) Google Scholar Nonalcoholic steatohepatitis (NASH), its severe form, can lead to cirrhosis or hepatocellular carcinoma.2Loomba R. Friedman S.L. Shulman G.I. Mechanisms and disease consequences of nonalcoholic fatty liver disease.Cell. 2021; 184: 2537-2564Abstract Full Text Full Text PDF PubMed Scopus (523) Google Scholar One strategy to reduce liver-related mortality is to prevent the progression of fibrogenesis, because hepatic fibrosis severity is one of the strongest prognostic indicators in chronic liver diseases, particularly NASH.3Tacke F. Puengel T. Loomba R. et al.An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH.J Hepatol. 2023; 79: 552-566Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Liver fibrosis is a complex process involving progressive accumulation of extracellular matrix (ECM) components, alterations in ECM degradation, and distortion of liver parenchyma in response to chronic damage. Fibrogenesis is driven primarily by the activation of hepatic stellate cells (HSCs), causing increased deposition of fibrillar ECM that negatively affects regeneration of the liver parenchyma over time.4Friedman S.L. Pinzani M. Hepatic fibrosis 2022: unmet needs and a blueprint for the future.Hepatology. 2022; 75: 473-488Crossref PubMed Scopus (100) Google Scholar Subsequently, identifying new targets to halt or reverse liver fibrogenesis holds promise as a possible treatment for NASH. The course of NAFLD varies owing to genetics, environmental factors, and divergent disease drivers. This variability makes it difficult to find effective drugs for all patients with NASH. The drug discovery process generally begins with treating cells in vitro, then moving to in vivo animal models, usually mice, before finally progressing to human clinical trials. A mouse NAFLD/NASH model would be useful if it can mimic the pathogenesis of human NAFLD/NASH. Mouse models are amenable to genetic dissection of complex traits, which helps identify potential genes and pathways for intervention in human beings. However, similar to the heterogeneity of human NAFLD/NASH, pathogenesis of NAFLD also varies significantly in different strains of mice in response to diet.5Hui S.T. Parks B.W. Org E. et al.The genetic architecture of NAFLD among inbred strains of mice.Elife. 2015; 4e05607Crossref Scopus (70) Google Scholar In this issue of Cellular and Molecular Gastroenterology and Hepatology, Hui et al6Hui S.T. Gong L. Swichkow C. et al.Role of matrix Gla protein in transforming growth factor-beta signaling and non-alcoholic steatohepatitis in mice.Cell Mol Gastroenterol Hepatol. 2023; https://doi.org/10.1016/j.jcmgh.2023.08.007Abstract Full Text Full Text PDF Google Scholar used an elegant hybrid mouse diversity panel that contains more than 100 inbred strains of mice. They used a \"systems genetics\" approach that integrated clinical and molecular traits with genetic mapping, correlating, and statistical modeling to identify matrix Gla protein (MGP) as a new target for NASH-associated fibrosis. MGP is a small secretory vitamin K–dependent protein highly expressed by vascular smooth muscle cells and chondrocytes. MGP activates bone morphogenic protein 2 and bone morphogenic protein 4, and acts as a calcification inhibitor in cartilage and vasculature. Homozygous MGP-knockout mice die at approximately 2 months old owing to aberrant cartilage and arterial calcification.7Cranenburg E.C. Koos R. Schurgers L.J. et al.Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species.Thromb Haemost. 2010; 104: 811-822C","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2023,"id":412540,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9612,"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":284312,"name":"Wen‐Xing Ding","orcid":"0000-0002-3167-5073","position":1,"is_corresponding":false},{"id":1193728,"name":"Kaitlyn Hinz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:50.261851Z","pmid":"37839467","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":[]}