- Gyorgy Baffy, MD, PhD
- Department of Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
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Special Issue Introduction
The biological functions of living cells and tissues are greatly affected by their physical microenvironment. There is a growing appreciation of the precise molecular and cellular mechanisms by which cells are able to detect, transmit and translate mechanical signals into biochemical responses. This process has been termed mechanotransduction, encompassing physical forces (e.g., compression, stretch, and shear) acting on cell surface mechanosensors (e.g., ion channels, transmembrane receptors, and adhesion molecules) that link mechanical impact to cytoskeleton structures (e.g., microtubules, actin, and intermediate filaments), and it may activate intracellular signaling cascades and yield pleiotropic mediators (e.g., nitric oxide, calcium, and reactive oxygen species) or engage developmental pathways (e.g., Wnt/beta-catenin, Hippo/YAP/TAZ, and Hedgehog) with complex genetic programs and cellular outcomes.
There is increasing evidence for the specific role of mechanotransduction in the pathogenesis of nonalcoholic fatty liver disease associated with metabolic dysfunction (NAFLD/MAFLD). Liver sinusoids represent a unique environment in which parenchymal hepatocytes, liver endothelial cells, hepatic stellate cells, and Kupffer cells have incredibly complex interactions as they are affected by the aberrant accumulation of lipid droplets, stiff extracellular matrix and liver fibrosis, and altered blood flow and pressure. Current research has begun to identify some of the key mechanosignaling pathways associated with the changing physical environment in NAFLD/MAFLD that could increasingly disrupt sinusoidal homeostasis and contribute to disease progression. These molecular mechanisms are associated with liver cell injury, inflammation, fibrosis, portal hypertension, and hepatocarcinogenesis, while it is expected that they will also provide novel targets for therapeutic interventions. It is our intention to make this special issue an important milestone in achieving this goal.
We welcome original or review manuscripts, perspectives, opinions, and commentary on different aspects to this special issue, including but not limited to:
Hepatic mechanosensors of lipid accumulation
Mechanotransduction and insulin resistance in fatty liver disease
Mechanosensitive pathways in sinusoidal endothelial dysfunction
Mechano-stress and the liver inflammatory response
Obesity, myosteatosis, and mechanotransduction
Mechanosignaling aspects of portal hypertension
Mechanotransduction and hepatocarcinogenesis
Gut microbiota and liver mechanosignaling
Liver genetic programs activated by mechanotransduction
Participants1.Gyorgy Baffy, Department of Medicine, VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
2.Moira Hilscher, Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
3.Piero Portincasa, Clinica Medica "A. Murri", Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, Bari, Italy.
Submission Deadline15 Mar 2023