Effect of human amniotic epithelial cells on pro-fibrogenic resident hepatic cells in a rat model of liver fibrosis

Autor: Ester Cotti Piccinelli, Ornella Parolini, Antonietta Silini, Luciana Barros Sant'Anna, Pietro Romele, V. Cesari, Serafina Farigu, I. Toschi, G. Vanosi, Marta Magatti, Anna Cargnoni, Patrizia Bonassi Signoroni
Rok vydání: 2017
Předmět:
0301 basic medicine
Liver Cirrhosis
biliary liver fibrosis
medicine.medical_treatment
ductular epithelial cells
placenta‐derived cells
Transforming Growth Factor beta
human amniotic membrane
Settore BIO/13 - BIOLOGIA APPLICATA
Liver injury
biology
Chemistry
Amniotic stem cells
Cell biology
Extracellular Matrix
Liver
human amniotic cells
Amniotic epithelial cells
cardiovascular system
Molecular Medicine
Female
Original Article
Myofibroblast
Epithelial-Mesenchymal Transition
bile duct ligation
myofibroblasts
03 medical and health sciences
medicine
Hepatic Stellate Cells
Animals
Humans
Epithelial–mesenchymal transition
Amnion
Rats
Wistar
Bile duct ligation
Biliary liver fibrosis
Ductular epithelial cells
Human amniotic cells
Human amniotic epithelial cells
Human amniotic membrane
Myofibroblasts
Placenta-derived cells
Cell Biology
Growth factor
Endothelial Cells
Epithelial Cells
Transforming growth factor beta
Original Articles
Fibroblasts
medicine.disease
human amniotic epithelial cells
Disease Models
Animal
030104 developmental biology
biology.protein
Hepatic stellate cell
Hepatocytes
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
Popis: Myofibroblasts are key fibrogenic cells responsible for excessive extracellular matrix synthesis characterizing the fibrotic lesion. In liver fibrosis, myofibroblasts derive either from activation of hepatic stellate cells (HSC) and portal fibroblasts (PF), or from the activation of fibroblasts that originate from ductular epithelial cells undergoing epithelial–mesenchymal transition. Ductular cells can also indirectly promote myofibroblast generation by activating TGF‐β, the main fibrogenic growth factor, through αvβ6 integrin. In addition, after liver injury, liver sinusoidal cells can lose their ability to maintain HSC quiescence, thus favouring HSC differentiation towards myofibroblasts. The amniotic membrane and epithelial cells (hAEC) derived thereof have been shown to decrease hepatic myofibroblast levels in rodents with liver fibrosis. In this study, in a rat model of liver fibrosis, we investigated the effects of hAEC on resident hepatic cells contributing to myofibroblast generation. Our data show that hAEC reduce myofibroblast numbers with a consequent reduction in fibronectin and collagen deposition. Interestingly, we show that hAEC strongly act on specific myofibroblast precursors. Specifically, hAEC reduce the activation of PF rather than HSC. In addition, hAEC target reactive ductular cells by inhibiting their proliferation and αvβ6 integrin expression, with a consequent decrease in TGF‐β activation. Moreover, hAEC counteract the transition of ductular cells towards fibroblasts, while it does not affect injury‐induced and fibrosis‐promoting sinusoidal alterations. In conclusion, among the emerging therapeutic applications of hAEC in liver diseases, their specific action on PF and ductular cells strongly suggests their application in liver injuries involving the expansion and activation of the portal compartment.
Databáze: OpenAIRE
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