Editorial: Liver Myofibroblasts

Liver Myofibroblasts Myofibroblasts (MFB) were first identified in the granulation tissue of healing wounds. They have features of both fibroblasts and smooth muscle cells. In contrast to fibroblasts they contain cytoplasmic actin microfilaments (stress fibers) connected to the extracellular matrix (ECM) by focal contacts. MFB are connected to each other by adherens and gap junctions. Mechanical forces produced by their contraction facilitate wound closure. Prominent stress fibers can be used to identify MFB in the tissue. They are of mesenchymal origin and are produced by activation and transdifferentiation of quiescent cell precursors after tissue injury. They are not found in normal liver but they appear in large numbers in damaged liver and become a major source of ECM proteins that replace functional tissue. MFB precursors in the liver are hepatic stellate cells (HSC), portal fibroblasts, and circulating bone marrow-derived collagen-producing cells (fibrocytes). They may also arise in a process termed epithelial-to-mesenchymal transition in which epithelial cells acquire a mesenchymal phenotype. Based on the important role of MFB, the knowledge of the transdifferentiation process is critical to understanding the development liver fibrosis. Profibrogenic and proinflammatory cytokines produced by macrophages and T cells regulate fibrogenesis. TGF-β1, the main profibrogenic cytokine, is also produced by MFB and stimulates ECM production in an autocrine manner. Mechanical factors play a role in fibrosis development. Tissue tension facilitates TGF-β1 production and α-smooth actin expression, which in turn increases tension development. MFB are susceptible to apoptosis, their disappearance is important for fibrosis reversibility, and they may be a target of anti-fibrogenic therapy. With the important role of MFB in the development of liver fibrosis in mind, leading experts in the field share their current perspectives on these cells in this Research Topic. As reviewed by Lepreux and Desmouliere, MFB are found in fetal liver and they reappear during liver injury. They are involved in tissue repair, in liver regeneration, and in liver cancer. HSC-derived MFB are studied in most cases. El Mourabit et al. have described a method to isolate MFB precursors from the rat biliary tree. These cells are highly proliferative and can be easily multiplied in vitro. Portal MFB differ in the expression of several genes from HSC-derived MFB, highlighting the distinct origin of the respective cell populations. Kawada concludes in his review that cytoglobin, a member of the mammalian globin family, is expressed in HSC and HSC-derived MFB but it is absent in MFB …