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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2022-04-01
|
| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/15/4/dmm049387 |
| _version_ | 1811257880227086336 |
|---|---|
| author | Sahar Keshvari Berit Genz Ngari Teakle Melanie Caruso Michelle F. Cestari Omkar L. Patkar Brian W. C. Tse Kamil A. Sokolowski Hilmar Ebersbach Julia Jascur Kelli P. A. MacDonald Gregory Miller Grant A. Ramm Allison R. Pettit Andrew D. Clouston Elizabeth E. Powell David A. Hume Katharine M. Irvine |
| author_facet | Sahar Keshvari Berit Genz Ngari Teakle Melanie Caruso Michelle F. Cestari Omkar L. Patkar Brian W. C. Tse Kamil A. Sokolowski Hilmar Ebersbach Julia Jascur Kelli P. A. MacDonald Gregory Miller Grant A. Ramm Allison R. Pettit Andrew D. Clouston Elizabeth E. Powell David A. Hume Katharine M. Irvine |
| author_sort | Sahar Keshvari |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T18:04:32Z |
| format | Article |
| id | doaj.art-9b4f9a4ccdaa4fd4b6ee2680c8ac5715 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-04-12T18:04:32Z |
| publishDate | 2022-04-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-9b4f9a4ccdaa4fd4b6ee2680c8ac57152022-12-22T03:22:02ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112022-04-0115410.1242/dmm.049387049387Therapeutic potential of macrophage colony-stimulating factor in chronic liver diseaseSahar Keshvari0Berit Genz1Ngari Teakle2Melanie Caruso3Michelle F. Cestari4Omkar L. Patkar5Brian W. C. Tse6Kamil A. Sokolowski7Hilmar Ebersbach8Julia Jascur9Kelli P. A. MacDonald10Gregory Miller11Grant A. Ramm12Allison R. Pettit13Andrew D. Clouston14Elizabeth E. Powell15David A. Hume16Katharine M. Irvine17 Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Preclinical Imaging Facility, Translational Research Institute, Brisbane, Queensland 4102, Australia Preclinical Imaging Facility, Translational Research Institute, Brisbane, Queensland 4102, Australia Novartis Institutes for Biomedical Research (NIBR), Fabrikstrasse 2, Novartis Campus, CH-4056 Basel, Switzerland Novartis Institutes for Biomedical Research (NIBR), Fabrikstrasse 2, Novartis Campus, CH-4056 Basel, Switzerland QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia Envoi Specialist Pathologists, Brisbane, Queensland 4059, Australia QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Envoi Specialist Pathologists, Brisbane, Queensland 4059, Australia Faculty of Medicine, The University of Queensland, Brisbane, Queensland 4006, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, Queensland 4102, Australia 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.http://dmm.biologists.org/content/15/4/dmm049387chronic liver diseaseliver regenerationfibrosis resolutioninflammationmacrophagesthioacetamidemouse |
| spellingShingle | Sahar Keshvari Berit Genz Ngari Teakle Melanie Caruso Michelle F. Cestari Omkar L. Patkar Brian W. C. Tse Kamil A. Sokolowski Hilmar Ebersbach Julia Jascur Kelli P. A. MacDonald Gregory Miller Grant A. Ramm Allison R. Pettit Andrew D. Clouston Elizabeth E. Powell David A. Hume Katharine M. Irvine Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease Disease Models & Mechanisms chronic liver disease liver regeneration fibrosis resolution inflammation macrophages thioacetamide mouse |
| title | Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease |
| title_full | Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease |
| title_fullStr | Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease |
| title_full_unstemmed | Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease |
| title_short | Therapeutic potential of macrophage colony-stimulating factor in chronic liver disease |
| title_sort | therapeutic potential of macrophage colony stimulating factor in chronic liver disease |
| topic | chronic liver disease liver regeneration fibrosis resolution inflammation macrophages thioacetamide mouse |
| url | http://dmm.biologists.org/content/15/4/dmm049387 |
| work_keys_str_mv | AT saharkeshvari therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT beritgenz therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT ngariteakle therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT melaniecaruso therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT michellefcestari therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT omkarlpatkar therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT brianwctse therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT kamilasokolowski therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT hilmarebersbach therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT juliajascur therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT kellipamacdonald therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT gregorymiller therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT grantaramm therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT allisonrpettit therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT andrewdclouston therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT elizabethepowell therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT davidahume therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease AT katharinemirvine therapeuticpotentialofmacrophagecolonystimulatingfactorinchronicliverdisease |