M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis

Cisplatin-induced nephrotoxicity leaded to apoptosis of tubular epithelial cells (ECs) and tubulointerstitial fibrosis through ROS stress and inflammatory cytokines. Tubulointerstitial fibrosis caused by cisplatin might be via activation of resident fibroblasts and epithelial-mesenchymal transition...

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Main Authors:	Yu, Chia-Cherng, Chien, Chiang-Ting, Chang, Tzu-Ching
Format:	Online
Language:	English
Published:	China Medical University 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752551/

id	pubmed-4752551
recordtype	oai_dc
spelling	pubmed-47525512016-02-16 M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis Yu, Chia-Cherng Chien, Chiang-Ting Chang, Tzu-Ching Original Article Cisplatin-induced nephrotoxicity leaded to apoptosis of tubular epithelial cells (ECs) and tubulointerstitial fibrosis through ROS stress and inflammatory cytokines. Tubulointerstitial fibrosis caused by cisplatin might be via activation of resident fibroblasts and epithelial-mesenchymal transition (EMT) of tubular ECs. Inflammatory niche was crucial for progression of fibroblast activation or EMT. It had been reported that M1/M2 macrophage polarization regulated pro-inflammation or pro-resolving phase in damage repairing. However, the role of macrophage polarization on cisplatin-induced EMT of tubular ECs had not been well elucidated. In this study, we used co-cultured cell model and condition medium to examine the interaction between tubular ECs, fibroblasts and M1/M2 macrophages. Our data showed that cisplatin alone induced incomplete EMT of tubular ECs, whereas fibroblasts co-cultured with cisplatin-treated ECs could lead to fibroblast activation by detection of α-SMA and collagen-1. Moreover, decrease of iNOS and increase of argenase-1 and CD206 expression indicated that macrophages co-cultured with cisplatin-treated ECs would turn to M2 phenotype. Finally, we found that condition medium of M2 macrophages could promote complete EMT of cisplatin-treated ECs. Taken together, cisplatin created an inflammatory niche via tubular ECs to activate fibroblasts and stimulated M2 macrophage polarization. M2 macrophages could turn back to promote EMT of cisplatin-treated ECs. These results revealed the cooperative roles of tubular ECs, fibroblast and M2 macrophages to facilitate the progression of renal fibroblasis. China Medical University 2016-02-22 /pmc/articles/PMC4752551/ /pubmed/26872813 http://dx.doi.org/10.7603/s40681-016-0005-5 Text en © China Medical University 2016
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Yu, Chia-Cherng Chien, Chiang-Ting Chang, Tzu-Ching
spellingShingle	Yu, Chia-Cherng Chien, Chiang-Ting Chang, Tzu-Ching M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis
author_facet	Yu, Chia-Cherng Chien, Chiang-Ting Chang, Tzu-Ching
author_sort	Yu, Chia-Cherng
title	M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis
title_short	M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis
title_full	M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis
title_fullStr	M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis
title_full_unstemmed	M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis
title_sort	m2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis
description	Cisplatin-induced nephrotoxicity leaded to apoptosis of tubular epithelial cells (ECs) and tubulointerstitial fibrosis through ROS stress and inflammatory cytokines. Tubulointerstitial fibrosis caused by cisplatin might be via activation of resident fibroblasts and epithelial-mesenchymal transition (EMT) of tubular ECs. Inflammatory niche was crucial for progression of fibroblast activation or EMT. It had been reported that M1/M2 macrophage polarization regulated pro-inflammation or pro-resolving phase in damage repairing. However, the role of macrophage polarization on cisplatin-induced EMT of tubular ECs had not been well elucidated. In this study, we used co-cultured cell model and condition medium to examine the interaction between tubular ECs, fibroblasts and M1/M2 macrophages. Our data showed that cisplatin alone induced incomplete EMT of tubular ECs, whereas fibroblasts co-cultured with cisplatin-treated ECs could lead to fibroblast activation by detection of α-SMA and collagen-1. Moreover, decrease of iNOS and increase of argenase-1 and CD206 expression indicated that macrophages co-cultured with cisplatin-treated ECs would turn to M2 phenotype. Finally, we found that condition medium of M2 macrophages could promote complete EMT of cisplatin-treated ECs. Taken together, cisplatin created an inflammatory niche via tubular ECs to activate fibroblasts and stimulated M2 macrophage polarization. M2 macrophages could turn back to promote EMT of cisplatin-treated ECs. These results revealed the cooperative roles of tubular ECs, fibroblast and M2 macrophages to facilitate the progression of renal fibroblasis.
publisher	China Medical University
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752551/
_version_	1613538172448276480

M2 macrophage polarization modulates epithelial-mesenchymal transition in cisplatin-induced tubulointerstitial fibrosis

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