@article{c68951042ce840a19a981f27da794d7f,
title = "Tuning macrophage phenotype to mitigate skeletal muscle fibrosis",
abstract = "Myeloid cells are critical to the development of fibrosis following muscle injury; however, the mechanism of their role in fibrosis formation remains unclear. In this study, we demonstrate that myeloid cell-derived TGF-b1 signaling is increased in a profibrotic ischemia reperfusion and cardiotoxin muscle injury model. We found that myeloid-specific deletion of Tgfb1 abrogates the fibrotic response in this injury model and reduces fibro/adipogenic progenitor cell proliferation while simultaneously enhancing muscle regeneration, which is abrogated by adaptive transfer of normal macrophages. Similarly, a murine TGFBRII-Fc ligand trap administered after injury significantly reduced muscle fibrosis and improved muscle regeneration. This study ultimately demonstrates that infiltrating myeloid cell TGF-b1 is responsible for the development of traumatic muscle fibrosis, and its blockade offers a promising therapeutic target for preventing muscle fibrosis after ischemic injury.",
author = "Stepien, {David M.} and Charles Hwang and Simone Marini and Pagani, {Chase A.} and Michael Sorkin and Visser, {Noelle D.} and Huber, {Amanda K.} and Edwards, {Nicole J.} and Loder, {Shawn J.} and Kaetlin Vasquez and Aguilar, {Carlos A.} and Ravi Kumar and Shamik Mascharak and Longaker, {Michael T.} and Jun Li and Benjamin Levi",
note = "Funding Information: D.M.S. was supported by a Plastic Surgery Foundation National Endowment Award, C.H. was supported by a Howard Hughes Medical Institute Medical Research Fellowship, and M.S. was supported by a Plastic Surgery Foundation National Endowment Award. B.L. was supported by National Institutes of Health (NIH)/National Institute of General Medical Sciences Grant K08GM109105, NIH Grant R01GM123069, an American College of Surgeons Clowes Award, U.S. Department of Defense Grants W81XWH-18-1-0653 (OR170174) and W81XWH-17-1-0655 (OR160105), and the International Fibrodysplasia Ossificans Progressiva Association. M.T.L. was funded by California Institute for Regenerative Medicine Clinical Fellow Training Grant TG2-01159, an American Society of Maxillofacial Surgeons/Maxillofacial Surgeons Foundation Research Grant Award, the Hagey Laboratory for Pediatric Regenerative Medicine, the Oak Foundation, NIH Grant U01 HL099776, and the Gunn/Olivier Fund. The Department of Radiology, the Center for Molecular Imaging, and the Preclinical Imaging and Computational Analysis Shared Resource at the University of Michigan are supported in part by Comprehensive Cancer Center NIH Grant P30 CA046592. Research reported in this article was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under Award P30 AR069620. Publisher Copyright: {\textcopyright} 2020 by The American Association of Immunologists, Inc.",
year = "2020",
month = apr,
day = "15",
doi = "10.4049/jimmunol.1900814",
language = "English",
volume = "204",
pages = "2203--2215",
journal = "Journal of Immunology",
issn = "0022-1767",
number = "8",
}