Details

Autor(en) / Beteiligte

• Stepien, David M
• Hwang, Charles
• Marini, Simone
• Pagani, Chase A
• Sorkin, Michael
• Visser, Noelle D
• Huber, Amanda K
• Edwards, Nicole J
• Loder, Shawn J
• Vasquez, Kaetlin
• Aguilar, Carlos A
• Kumar, Ravi
• Mascharak, Shamik
• Longaker, Michael T
• Li, Jun
• Levi, Benjamin

Titel

Tuning Macrophage Phenotype to Mitigate Skeletal Muscle Fibrosis

Ist Teil von

• The Journal of immunology (1950), 2020-04, Vol.204 (8), p.2203-2215

Ort / Verlag

United States

Erscheinungsjahr

2020

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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-β1 signaling is increased in a profibrotic ischemia reperfusion and cardiotoxin muscle injury model. We found that myeloid-specific deletion of 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-β1 is responsible for the development of traumatic muscle fibrosis, and its blockade offers a promising therapeutic target for preventing muscle fibrosis after ischemic injury.