Liver Fibrosis—From Mechanisms of Injury to Modulation of Disease

Abstract

The Transregional Collaborative Research Center “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (referred to as SFB/TRR57) was funded for 13 years (2009–2021) by the German Research Council (DFG). This consortium was hosted by the Medical Schools of the RWTH Aachen University and Bonn University in Germany. The SFB/TRR57 implemented combined basic and clinical research to achieve detailed knowledge in three selected key questions: (i) What are the relevant mechanisms and signal pathways required for initiating organ fibrosis? (ii) Which immunological mechanisms and molecules contribute to organ fibrosis? and (iii) How can organ fibrosis be modulated, e.g., by interventional strategies including imaging and pharmacological approaches? In this review we will summarize the liver-related key findings of this consortium gained within the last 12 years on these three aspects of liver fibrogenesis. We will highlight the role of cell death and cell cycle pathways as well as nutritional and iron-related mechanisms for liver fibrosis initiation. Moreover, we will define and characterize the major immune cell compartments relevant for liver fibrogenesis, and finally point to potential signaling pathways and pharmacological targets that turned out to be suitable to develop novel approaches for improved therapy and diagnosis of liver fibrosis. In summary, this review will provide a comprehensive overview about the knowledge on liver fibrogenesis and its potential therapy gained by the SFB/TRR57 consortium within the last decade. The kidney-related research results obtained by the same consortium are highlighted in an article published back-to-back in Frontiers in Medicine.

Differential Staining Patterns for Evaluation of Ovarian and Oviducts Fibrosis Using the Polarized Light Microscope and the Digital Images Analysis

“…(3) Our work can recommend polarizing microscope as a tool to evaluate fibrosis of ovary and oviducts, as it is a cheap, less bulky, and user friendly tool. (4) Polarizing microscope can differentiate between different collagen patterns, as mature thick type I collagen appeared with orange to red color, while thin immature collagen type III was green in color. However, studies are still needed to be able to recommend polarizing microscopy for demonstrating of fibrosis in different organs.…”

“…Fibrosis is commonly demonstrated in different organs as heart, kidney, lungs, liver, and testis. Without effective treatment, fibrosis impaired organ function and ultimately induces organ malfunction [1][2][3][4] . Fibrosis is characterized by excessive scaring formation instead of normal tissue, which then finally results in the destruction of the tissue architecture and organ remodeling.…”

Sjögren’s Syndrome-Related Organs Fibrosis: Hypotheses and Realities

“…Autoimmune hepatitis is the second leading cause of liver damage in SS patients [ 47 ]. Liver fibrotic processes depend on the activation of an initial injury of hepatocytes by autoreactive immunological phenomena; these events lead to the proliferation of myofibroblasts and the activation of stellate cells [ 48 ]. These manifestations may, in turn, accelerate the deposition of collagen or glycoproteins in the liver, leading to liver fibrosis that interferes with the liver function and contributes to gradual organ failure [ 49 ].…”

γδ T cells: The potential role in liver disease and implications for cancer immunotherapy

“…32 In addition, hepatic fibrosis might be regulated by cytokines and chemokines. 45 IL-17 is an essential regulatory cytokine in liver inflammation, and γδ T cells accumulate in fibrotic livers and contribute to IL-17 secretion in chronic hepatitis patients. 46,47 A previous study revealed that in a Schistosoma japonicum-infected C57BL/6 mouse model, γδ T cells mediate the recruitment of neutrophils to the liver and induce liver fibrosis with IL-17 production.…”

“…A study reported that a decrease in the number of γδ T cells in the peripheral blood and liver is significantly associated with the severity of fibrosis 32 . In addition, hepatic fibrosis might be regulated by cytokines and chemokines 45 . IL‐17 is an essential regulatory cytokine in liver inflammation, and γδ T cells accumulate in fibrotic livers and contribute to IL‐17 secretion in chronic hepatitis patients 46,47 .…”