Interaction of macrophages with apoptotic cells inhibits transdifferentiation and invasion of lung fibroblasts
- 주제(키워드) apoptotic cells , macrophages , lung fibroblasts , myofibroblast , invasion
- 주제(기타) Oncology
- 주제(기타) Cell Biology
- 등재 SCOPUS
- 발행기관 IMPACT JOURNALS LLC
- 발행년도 2017
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000161786
- 본문언어 영어
- Published As http://dx.doi.org/10.18632/oncotarget.22737
초록/요약
The invasion of activated fibroblasts is a key mechanism of tissue fibrosis pathology. The recognition and uptake of apoptotic cells can induce the anti-fibrogenic programming of macrophages. We demonstrate that after interacting with apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF-beta 1-induced increases in myofibroblast (fibroproliferative) phenotypic markers and reduce the enhanced invasive capacity of TGF-beta 1- or EGF-treated mouse lung fibroblasts (MLg). Furthermore, numerous treatment strategies prevented the anti-fibrotic effects of conditioned media, including transfection of macrophages with COX-2 or RhoA siRNAs or treatment of MLg cells with receptor antagonists for prostaglandin E-2 (PGE(2)), PGD(2), or hepatocyte growth factor (HGF). Additionally, administration of apoptotic cells in vivo inhibited the bleomycin-mediated invasive capacity of primary fibroblasts, as well as adhesion and extracellular matrix protein mRNA expression. These data suggest that the anti-fibrogenic programming of macrophages by apoptotic cells can be used as a novel tool to control the progressive fibrotic reaction.
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