Interaction of macrophages with apoptotic cells inhibits transdifferentiation and invasion of lung fibroblasts
- 주제(키워드) Apoptotic cells , Invasion , Lung fibroblasts , Macrophages , Myofibroblast
- 후원정보 Ministry of Science, ICT and Future Planning
- 등재 SCIE, SCOPUS
- 발행기관 Impact Journals LLC
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000156129
- 본문언어 영어
- Published As http://dx.doi.org/10.18632/oncotarget.22737
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
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 antifibrogenic programming of macrophages. We demonstrate that after interacting with apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF-β1-induced increases in myofibroblast (fibroproliferative) phenotypic markers and reduce the enhanced invasive capacity of TGF-β1- 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 E2 (PGE2), PGD2, 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. © Kim et al.
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