Morphogen-related therapeutic targets for liver fibrosis - 29/09/15
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Summary |
Recent research on hepatic stellate cells (HSCs) has spotlighted the involvement of morphogens in their cell fate determination in liver fibrosis. Temporally and spatially expressed during embryonic development, morphogens are involved in regulation of cell proliferation and differentiation, and tissue patterning. In normal adult liver, morphogens are generally expressed at low levels. However, in liver disease, myofibroblastic HSCs express morphogens such as Wnt, Shh, Necdin, DLK1, and Notch as part of their participation in fibrogenesis and wound healing. Liver regeneration involves cell proliferation and differentiation akin to embryonic liver development where the cells appear to undergo similar fates, and not surprisingly the morphogens are re-activated for the regenerative purpose in adult liver injury. Evidence also points to crosstalk of these morphogens in regulation of HSC fate determination. Genetic ablation or pharmacologic inhibition of morphogens reverts activated HSC to quiescent cells in culture and attenuates progression of hepatic fibrosis. However, positive regulation of liver regeneration by the morphogens needs to be spared. Therapeutically, manipulation of morphogen activities in a cell type and phase-specific manner should offer new modalities for chronic liver disease.
Le texte complet de cet article est disponible en PDF.Abbreviations : CCL4, C/EBPa, CTGF, Dlk1, ERK1/2, FGF18, Gfap, Gli1, Hes-1, HGF, IGF, IL, PAF, PDGF, Pref-1, Ptn, p75Ntr, RBPjk, Rho, Shh, Sox9, TGF, TNF
Plan
☆ | This article is part of the special issue “Alcohol, Virus and Steatosis evolving to cancer” featuring the conference papers of the 10th International Symposium organized by the Brazilian Society of Hepatology in São Paulo, Brazil, September 30th–October 1st, 2015. |
☆☆ | The studies described in this review have been supported by NIAAA grants (P50AA011999, R24AA012885, U01AA018663) and Medical Research Service of Department of Veterans Affairs (VA Merit Review: 1I01BX001991 and senior research career scientist award). |
Vol 39 - N° S1
P. S69-S74 - septembre 2015 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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