ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway

Sha,Hao; Zhang,Dianzhong; Zhang,Yunfei; Wen,Yanhua; Wang,Yucai

doi:10.3892/mmr.2017.6992

ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway

Authors:
- Hao Sha
- Dianzhong Zhang
- Yunfei Zhang
- Yanhua Wen
- Yucai Wang
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Affiliations: Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
Published online on: July 14, 2017 https://doi.org/10.3892/mmr.2017.6992
Pages: 3641-3647

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Abstract

There are different polarization states of macrophages, including the classically activated M1 phenotype and the alternatively activated M2 phenotype. These have different functions in the inflammation process. Activating transcription factor 3 (ATF3) is a key transcriptional regulator that inhibits the inflammatory response. However, the effects of ATF3 on migration and anti‑inflammatory control mechanisms of macrophages have not been thoroughly investigated. The present study investigated the effect of ATF3 on macrophage migration and M1/M2 polarization. Results revealed that overexpression of ATF3 promoted macrophage migration and the expression of the M2 phenotype markers [cluster of differentiation (CD) 163, mannose receptor C type 1, arginase 1 and peroxisome proliferator‑activated receptor γ] and inhibited expression of the M1 phenotype markers (monocyte chemoattractant protein‑1, inducible nitric oxide synthase, CD16 and tumor necrosis factor‑α), whereas knockdown of ATF3 resulted in a contrary effect. In addition, the wingless‑type MMTV integration site family member (Wnt)/β‑catenin signaling pathway was activated and the expression level of tenascin (TNC) was significantly upregulated by overexpression of ATF3. Additionally, inhibition of Wnt/β‑catenin signaling significantly attenuated the upregulatory effect of ATF3 on TNC. Finally, the effect of ATF3 on macrophage migration and markers of the M1 or M2 state was investigated using TNC‑specific siRNA. In conclusion, the results of the present study suggested that ATF3 promotes macrophage migration and reverses M1‑polarized macrophages to the M2 phenotype by upregulation of TNC via the Wnt/β‑catenin signaling pathway.

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