Deciphering the Matrisome: Extracellular Matrix Remodeling in Liver Cirrhosis and Hepatocellular Carcinoma.

Liver cirrhosis and hepatocellular carcinoma (HCC) are major public health concerns due to their high morbidity and mortality rates. The liver, a vital organ for metabolism, detoxification, and homeostasis, depends on the matrisome, a complex and dynamic network of extracellular matrix (ECM) components for maintaining structural and functional integrity. Chronic liver inflammation, induced by factors such as alcohol abuse, viral hepatitis, and non-alcoholic fatty liver disease, leads to fibrosis and cirrhosis, progressing to HCC. The matrisome, composed of ECM proteins including collagen, fibronectin, and laminin, plays a critical role in regulating tissue homeostasis, cell signaling, and tissue repair. Dysregulation of ECM components contributes to the pathogenesis of both liver cirrhosis and cancer. In cirrhosis, matrisome alterations are characterized by excessive ECM deposition and fibrosis, which disrupt the liver's architecture and impair its function. Activated hepatic stellate cells (HSCs) are the principal mediators of fibrosis, producing large quantities of ECM components. In liver cancer, matrisome remodeling facilitates tumorigenesis by promoting cancer cell proliferation, invasion, and metastasis. The tumor microenvironment, shaped by ECM alterations, further supports tumor growth and dissemination. Matrix metalloproteinases (MMPs) play a pivotal role in ECM degradation, fibrosis progression, and tumor invasion, while tissue inhibitors of metalloproteinases (TIMPs) modulate MMP activity. A comprehensive understanding of the molecular mechanisms that link matrisome alterations with the progression from cirrhosis to liver cancer is essential for identifying novel diagnostic and therapeutic targets. This review highlights the dynamic responses of the hepatic matrisome to both acute and chronic insults, emphasizing the complex interplay between ECM components, cellular behavior, and disease progression. Elucidating these interactions may inform strategies aimed at improving clinical outcomes for patients with liver cirrhosis and HCC.