When healing turns into killing – the pathophysiology of pancreatic and hepatic fibrosis. (4th May 2022)

• Record Type: Journal Article
• Authors: Ferdek, Pawel E.; Krzysztofik, Daria; Stopa, Kinga B.; Kusiak, Agnieszka A.; Paw, Milena; Wnuk, Dawid; Jakubowska, Monika A.
• Is Part Of: Journal of physiology. Volume 600:Number 11(2022)
• Page Start: 2579
• Page End: 2612
• Publication Date: 2022-05-04
• Subjects: fibrosis -- fibroblasts -- liver -- pancreas -- stellate cells; Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP281135
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract: Disorders such as pancreatic or hepatic fibrosis are a cruel reminder that disruption of the delicate physiological balance could result in severe pathological consequences. Fibrosis is usually associated with chronic diseases and manifests itself as excessive deposition of the extracellular matrix, which gradually leads to the replacement of the cellular components by fibrotic lesions, significantly compromising normal tissue functions. The main cellular mediators of fibrosis are different populations of tissue fibroblasts, predominantly hepatic and pancreatic stellate cells in the liver and pancreas, respectively. These cells undergo a phenotypic switch in response to (bio)chemical or physical stimuli and acquire a myofibroblast‐like phenotype characterised by increased contractile and adhesive properties, elevated expression of certain cytoskeletal and membrane proteins, and prominent production of extracellular matrix components. In the past few decades, a substantial scientific effort has been undertaken to investigate the pathogenesis of fibrosis. Here, cellular mechanisms of hepatic and pancreatic fibrosis, their aetiological factors, associated diseases and prospective therapies are discussed. New therapies against fibrosis are likely to be focused on regulation of hepatic/pancreatic stellate cell physiology as well as normalisation of the organ mechanostasis. Abstract : Abstract figure legend While the liver and pancreas differ in their morphology and functions, the mechanisms underlying hepatic and pancreatic fibrosis are remarkably similar. Chronic persistent injury, often associated with alcohol/drug abuse, cigarette smoking, viral infections or genetic predispositions, results in phenotyping transition of hepatic/pancreatic stellate cells from their quiescent into activated myofibroblast‐like phenotype. Activated stellate cells contribute to excessive deposition of the extracellular matrix, which compromises normal tissue architecture and impairs its physiological functions.