Current Pathobiology Reports 

About: Current Pathobiology Reports is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Fibrosis & Hepatic stellate cell. It has an ISSN identifier of 2167-485X. Over the lifetime, 222 publications have been published receiving 4018 citations. The journal is also known as: Curr pathobiol rep.

TNFα in liver fibrosis.

Abstract: Hepatocyte death, inflammation, and liver fibrosis are the hallmarks of chronic liver disease. Tumor necrosis factor-α (TNFα) is an inflammatory cytokine involved in liver inflammation and sustained liver inflammation leads to liver fibrosis. TNFα exerts inflammation, proliferation, and apoptosis. However, the role of TNFα signaling in liver fibrosis is not fully understood. This review highlights the recent findings demonstrating the molecular mechanisms of TNFα and its downstream signaling in liver fibrosis. During the progression of liver fibrosis, hepatic stellate cells play a pivotal role in a dynamic process of production of extracellular matrix proteins and modulation of immune response. Hepatic stellate cells transdifferentiate into activated myofibroblasts in response to damaged hepatocyte-derived mediators and immune cell-derived cytokines/chemokines. Here, we will discuss the role of TNFα in hepatic stellate cell survival and activation and the crosstalk between hepatic stellate cells and hepatocytes or other immune cells, such as macrophages, dendritic cells, and B cells in the development of liver fibrosis.

Autophagy and Ferroptosis—What Is the Connection?

Abstract: Purpose of Review Autophagy is a conserved intracellular degradation system and plays a dual role in cell death, depending on context and phase. Ferroptosis is a new form of regulated cell death that mainly depends on iron accumulation and lipid peroxidation. In this review, we summarize the processes of autophagy and ferroptosis and discuss their crosstalk mechanisms at the molecular level.

TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis: Updated

Abstract: TGF-β is a pro-fibrogenic and antiproliferative protein with multiple functions depending on the cellular context. In liver fibrosis, TGF-β was identified as very robust driver of hepatic stellate cell (HSC) activation and extracellular matrix production, and a plethora of approaches targeting the TGF-β signaling pathway were successfully used to tackle fibrogenesis in animal models of chronic liver diseases. The present review builds on knowledge of the last two decades about TGF-β function in myofibroblast generation and fibrogenesis, and presents the milestone discoveries from the recent 3–5 years. These include findings on downstream targets with fibrogenic function, pathways that facilitate TGF-β expression in HSC, and miRNAs regulated by or regulating the TGF-β pathway. Further, recent data on TGF-β signaling, its integration with other pathways, and TGF-β signaling regulators identified in the setting of fibrotic liver disease are provided. Additionally, we will discuss TGF-β and epithelial-to-mesenchymal transition in liver fibrosis, and what we have learned from other fibrotic diseases, besides liver. Finally, challenges and opportunities for TGF-β-directed therapies in HSC activation, liver fibrosis, and disease progression are discussed.

Beclin 1, an Essential Component and Master Regulator of PI3K-III in Health and Disease.

Abstract: Autophagy is a cell 'self-digestion' pathway involving the synthesis, trafficking and delivery of autophagosomes to lysosomes for degradation. Beclin 1 is a core component of the class III phosphatidylinositol 3-kinase (PI3K-III) complex, which plays an important role in membrane trafficking and restructuring involved in autophagy, endocytosis, cytokinesis and phagocytosis. To date Beclin 1 has largely been characterized in the context of autophagy; it modulates the lipid kinase activity of PI3K-III catalytic unit VPS34, which generates phosphatidylinositol 3-phosphate (PI(3)P), enabling the recruitment of a number of autophagy proteins involved in the nucleation of the autophagosome. Beclin 1 seems to function as an adaptor for recruiting multiple proteins that modulate VPS34. The recent identification of Beclin 1 protein modifications has shed light on its regulation in autophagy, and the discovery of non-autophagy functions of Beclin 1 has expanded our view of Beclin 1's involvement in tissue homeostasis and human diseases.

Reversibility of Liver Fibrosis and Inactivation of Fibrogenic Myofibroblasts

Abstract: Many studies have demonstrated that hepatic fibrosis is reversible. Regression of liver fibrosis is associated with resorption of fibrous scar and the disappearance of collagen-producing myofibroblasts. The fate of these myofibroblasts has been recently revealed: some myofibroblasts undergo senescence and apoptosis during reversal of fibrosis, whereas other myofibroblasts revert to a quiescent-like phenotype. Inactivation of myofibroblasts is a newly described phenomenon (Kisseleva et al. in Proc. Natl .Acad. Sci. USA 109:9448–9453, 2012) which now requires mechanistic investigation. Understanding the mechanism of inactivation of hepatic stellate cells on cessation of fibrogenic stimuli may identify new approaches to cause already existing activated hepatic stellate cells/myofibroblasts to revert to a quiescent-like state. This review summarizes the research on the inactivation of hepatic myofibroblasts.