CD47 in the development and progression of MASLD/MASH (IMAGE)
Caption
(A) Elevated expression of CD47 on necroptotic hepatocytes interacts with SIRPα on liver-resident Kupffer cells and infiltrating macrophages, inhibiting phagocytosis of damaged hepatocytes and contributing to liver inflammation and the progression of MASH. (B) CD47 is elevated on HSCs in mice fed high-fat diet. A novel YAP/TEAD4 binds to the CD47 promoter to enhance CD47 expression, leading to HSC activation and excessive production of extracellular matrix proteins, thereby exacerbating liver fibrosis. (C) TSP1 association with CD47 on LSECs triggers activation of the Rho-ROCK-myosin pathway, leading to defenestration. This impairs the exchange of nutrients and waste between hepatocytes and the intravascular compartment, contributing to liver fibrosis and the progression of MASH. This figure is created using Biorender.com. CD47, cluster of differentiation 47; HSCs, hepatic stellate cells; LSECs, liver sinusoidal endothelial cells; MASH, metabolic dysfunction-associated steatohepatitis; MASLD, metabolic dysfunction-associated steatotic liver disease; Rho, ras homologous; ROCK, rho-associated coiled-coil containing protein kinase; SIRPα, signal regulatory protein alpha; TEAD4, TEA domain transcription factor 4; TSP1, thrombospondin-1; YAP, yes-associated protein.
Credit
By Josephine Otuagomah, Alana Newcomb, Taesik Gwag, and Shuxia Wang.
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Credit must be given to the creator. Only noncommercial uses of the work are permitted.
License
CC BY-NC