Research Papers:

Interaction of macrophages with apoptotic cells inhibits transdifferentiation and invasion of lung fibroblasts

Yong-Bae Kim, Young-So Yoon, Youn-Hee Choi, Eun-Mi Park and Jihee Lee Kang _

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Oncotarget. 2017; 8:112297-112312. https://doi.org/10.18632/oncotarget.22737

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Yong-Bae Kim1, Young-So Yoon1,2, Youn-Hee Choi1,2, Eun-Mi Park1,3 and Jihee Lee Kang1,2

1Tissue Injury Defense Research Center, College of Medicine, Ewha Womans University, Seoul 07985, Korea

2Department of Physiology, College of Medicine, Ewha Womans University, Seoul 07985, Korea

3Department of Pharmacology, College of Medicine, Ewha Womans University, Seoul 07985, Korea

Correspondence to:

Jihee Lee Kang, email: [email protected]

Keywords: apoptotic cells; macrophages; lung fibroblasts; myofibroblast; invasion

Received: September 01, 2017     Accepted: November 15, 2017     Published: November 28, 2017


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-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.

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