{"title":"ECM1:一种具有抗纤维化潜力的新型基质细胞蛋白","authors":"Isabel Fabregat, Francisco Javier Cubero","doi":"10.1136/gutjnl-2024-333455","DOIUrl":null,"url":null,"abstract":"Although numerous compounds that target individual or multiple cells or pathways have demonstrated antifibrotic potential, the reality is that only a small number of candidates have progressed successfully to the clinical trials phase. It seems plausible that the development of antifibrotic therapies focusing on the removal of fibrosis-causing agents and factors affecting hepatic stellate cell (HSC) activation might hold promise for reducing and preventing liver disease. Moreover, these therapies need to be safe with little or no hepatotoxicity and/or adverse effects. In liver homoeostasis, transforming growth factor-beta (TGF-β) is secreted in a biologically inactive, the so-called latent TGF-β form (LTGF-β) associated in a non-covalent complex with the extracellular matrix (ECM).1 In response to injury, local LTGF-β complexes are converted into active TGF-β. Activation of LTGF-β is mediated by several signals, including integrins, thrombospondin, proteases and reactive oxygen species.2 During liver fibrosis, TGF-β acts as a master profibrogenic cytokine in promoting activation and myofibroblastic differentiation of HSC, a central event in liver fibrogenesis and ECM production.3 Therefore, the regulation of locally activated TGF-β levels might be an excellent therapeutic target for liver fibrogenesis. ECM protein-1 (ECM1) was recently identified2 as a critical gatekeeper in the healthy liver, contributing to normal architecture and physiological homoeostasis of cell–cell communication by …","PeriodicalId":12825,"journal":{"name":"Gut","volume":"8 1","pages":""},"PeriodicalIF":23.0000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ECM1: a novel matricellular protein with promising antifibrotic potential\",\"authors\":\"Isabel Fabregat, Francisco Javier Cubero\",\"doi\":\"10.1136/gutjnl-2024-333455\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Although numerous compounds that target individual or multiple cells or pathways have demonstrated antifibrotic potential, the reality is that only a small number of candidates have progressed successfully to the clinical trials phase. It seems plausible that the development of antifibrotic therapies focusing on the removal of fibrosis-causing agents and factors affecting hepatic stellate cell (HSC) activation might hold promise for reducing and preventing liver disease. Moreover, these therapies need to be safe with little or no hepatotoxicity and/or adverse effects. In liver homoeostasis, transforming growth factor-beta (TGF-β) is secreted in a biologically inactive, the so-called latent TGF-β form (LTGF-β) associated in a non-covalent complex with the extracellular matrix (ECM).1 In response to injury, local LTGF-β complexes are converted into active TGF-β. Activation of LTGF-β is mediated by several signals, including integrins, thrombospondin, proteases and reactive oxygen species.2 During liver fibrosis, TGF-β acts as a master profibrogenic cytokine in promoting activation and myofibroblastic differentiation of HSC, a central event in liver fibrogenesis and ECM production.3 Therefore, the regulation of locally activated TGF-β levels might be an excellent therapeutic target for liver fibrogenesis. ECM protein-1 (ECM1) was recently identified2 as a critical gatekeeper in the healthy liver, contributing to normal architecture and physiological homoeostasis of cell–cell communication by …\",\"PeriodicalId\":12825,\"journal\":{\"name\":\"Gut\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":23.0000,\"publicationDate\":\"2024-10-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gut\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/gutjnl-2024-333455\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/gutjnl-2024-333455","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
ECM1: a novel matricellular protein with promising antifibrotic potential
Although numerous compounds that target individual or multiple cells or pathways have demonstrated antifibrotic potential, the reality is that only a small number of candidates have progressed successfully to the clinical trials phase. It seems plausible that the development of antifibrotic therapies focusing on the removal of fibrosis-causing agents and factors affecting hepatic stellate cell (HSC) activation might hold promise for reducing and preventing liver disease. Moreover, these therapies need to be safe with little or no hepatotoxicity and/or adverse effects. In liver homoeostasis, transforming growth factor-beta (TGF-β) is secreted in a biologically inactive, the so-called latent TGF-β form (LTGF-β) associated in a non-covalent complex with the extracellular matrix (ECM).1 In response to injury, local LTGF-β complexes are converted into active TGF-β. Activation of LTGF-β is mediated by several signals, including integrins, thrombospondin, proteases and reactive oxygen species.2 During liver fibrosis, TGF-β acts as a master profibrogenic cytokine in promoting activation and myofibroblastic differentiation of HSC, a central event in liver fibrogenesis and ECM production.3 Therefore, the regulation of locally activated TGF-β levels might be an excellent therapeutic target for liver fibrogenesis. ECM protein-1 (ECM1) was recently identified2 as a critical gatekeeper in the healthy liver, contributing to normal architecture and physiological homoeostasis of cell–cell communication by …
期刊介绍:
Gut is a renowned international journal specializing in gastroenterology and hepatology, known for its high-quality clinical research covering the alimentary tract, liver, biliary tree, and pancreas. It offers authoritative and current coverage across all aspects of gastroenterology and hepatology, featuring articles on emerging disease mechanisms and innovative diagnostic and therapeutic approaches authored by leading experts.
As the flagship journal of BMJ's gastroenterology portfolio, Gut is accompanied by two companion journals: Frontline Gastroenterology, focusing on education and practice-oriented papers, and BMJ Open Gastroenterology for open access original research.