Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease

Resident and recruited macrophages control the development and proliferation of the liver. We have previously shown in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepati...

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Автори: Sahar Keshvari (Автор), Berit Genz (Автор), Ngari Teakle (Автор), Melanie Caruso (Автор), Michelle F. Cestari (Автор), Omkar L. Patkar (Автор), Brian W. C. Tse (Автор), Kamil A. Sokolowski (Автор), Hilmar Ebersbach (Автор), Julia Jascur (Автор), Kelli P. A. MacDonald (Автор), Gregory Miller (Автор), Grant A. Ramm (Автор), Allison R. Pettit (Автор), Andrew D. Clouston (Автор), Elizabeth E. Powell (Автор), David A. Hume (Автор), Katharine M. Irvine (Автор)
Формат: Книга
Опубліковано: The Company of Biologists, 2022-04-01T00:00:00Z.
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Резюме:Resident and recruited macrophages control the development and proliferation of the liver. We have previously shown in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here, we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, using a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodelling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.
Опис примірника:1754-8403
1754-8411
10.1242/dmm.049387