Ecm1, or extracellular matrix protein 1, is a glycoprotein that interacts with extracellular and structural proteins. It plays a crucial role in maintaining the extracellular matrix and is involved in various biological processes, including regulation of cytokine activation and cell-cell interactions. Its associated pathways include the TGF-β signaling pathway, which is pivotal in fibrosis and cell activation [2,4]. Genetic models, such as knockout (KO) mice, have been instrumental in understanding Ecm1's function.

In liver fibrosis studies, Ecm1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. Ecm1 was found to stabilize extracellular matrix-deposited TGF-β in its inactive form by interacting with αv integrins, preventing activation of hepatic stellate cells (HSCs) [2]. In hepatocyte-specific Ecm1-deficient mice, the antifibrotic effect of Salvianolic acid B was abolished, indicating that Ecm1 is a key target for this compound in alleviating liver fibrosis by inhibiting hepatocyte ferroptosis [1]. In macrophages, macrophage-specific knockout of Ecm1 resulted in increased arginase 1 expression and impaired polarization into the M1 macrophage phenotype after lipopolysaccharide treatment, highlighting its role in inflammation and tissue repair in the intestine during inflammatory bowel disease [3].

In conclusion, Ecm1 is essential for maintaining tissue homeostasis, particularly in preventing fibrosis in the liver by regulating TGF-β activation. The use of Ecm1 KO and conditional knockout (CKO) mouse models has significantly enhanced our understanding of its role in liver fibrosis and inflammatory bowel disease, offering potential therapeutic targets for these diseases.

References:

1. Fu, Yadong, Zhou, Xiaoxi, Wang, Lin, Sun, Bing, Liu, Ping. 2024. Salvianolic acid B attenuates liver fibrosis by targeting Ecm1 and inhibiting hepatocyte ferroptosis. In Redox biology, 69, 103029. doi:10.1016/j.redox.2024.103029. https://pubmed.ncbi.nlm.nih.gov/38184998/

2. Fan, Weiguo, Liu, Tianhui, Chen, Wen, Jia, Jidong, Sun, Bing. 2019. ECM1 Prevents Activation of Transforming Growth Factor β, Hepatic Stellate Cells, and Fibrogenesis in Mice. In Gastroenterology, 157, 1352-1367.e13. doi:10.1053/j.gastro.2019.07.036. https://pubmed.ncbi.nlm.nih.gov/31362006/

3. Zhang, Yaguang, Li, Xuezhen, Luo, Zhongguang, Liu, Jie, Sun, Bing. 2020. ECM1 is an essential factor for the determination of M1 macrophage polarization in IBD in response to LPS stimulation. In Proceedings of the National Academy of Sciences of the United States of America, 117, 3083-3092. doi:10.1073/pnas.1912774117. https://pubmed.ncbi.nlm.nih.gov/31980528/

4. Link, Frederik, Li, Yujia, Zhao, Jieling, Dooley, Steven, Wang, Sai. 2025. ECM1 attenuates hepatic fibrosis by interfering with mediators of latent TGF-β1 activation. In Gut, 74, 424-439. doi:10.1136/gutjnl-2024-333213. https://pubmed.ncbi.nlm.nih.gov/39448254/