Impact of heterogeneity in liver matrix and intrahepatic cells on the progression of hepatic fibrosis

Abstract

Liver fibrosis is a disease with a high prevalence worldwide. The development of hepatic fibrosis results from a combination of factors within the liver, such as extracellular matrix (ECM) deposition, hepatic stellate cells (HSCs) activation, collagen cross-linking, and inflammatory response. Heterogeneity in fibrotic liver is the result of a combination of heterogeneity in the intrahepatic microenvironment as well as heterogeneous expression of fibrosis-associated enzymes and cells, complicating the study of the mechanisms underlying the progression of liver fibrosis. The role of this heterogeneity on the crosstalk between cells and matrix and on the fibrotic process is worth exploring. In this paper, we will describe the phenomenon and mechanism of heterogeneity of liver matrix and intrahepatic cells in the process of hepatic fibrosis and discuss the crosstalk between heterogeneous factors on the development of fibrosis. The elucidation of heterogeneity is important for a deeper understanding of the pathological mechanisms of liver fibrosis as well as for clinical diagnosis and targeted therapies.