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Article

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
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China
  • Pages: 3641-3647
    |
    Published online on: July 14, 2017
       https://doi.org/10.3892/mmr.2017.6992
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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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1 

Gordon S and Martinez FO: Alternative activation of macrophages: Mechanism and functions. Immunity. 32:593–604. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Martinez FO, Sica A, Mantovani A and Locati M: Macrophage activation and polarization. Front Biosci. 13:453–461. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Kuroda E, Ho V, Ruschmann J, Antignano F, Hamilton M, Rauh MJ, Antov A, Flavell RA, Sly LM and Krystal G: SHIP represses the generation of IL-3-induced M2 macrophages by inhibiting IL-4 production from basophils. J Immunol. 183:3652–3660. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Odegaard JI and Chawla A: Mechanisms of macrophage activation in obesity-induced insulin resistance. Nat Clin Pract Endocrinol Metab. 4:619–626. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Porcheray F, Viaud S, Rimaniol AC, Léone C, Samah B, Dereuddre-Bosquet N, Dormont D and Gras G: Macrophage activation switching: An asset for the resolution of inflammation. Clin Exp Immunol. 142:481–489. 2005.PubMed/NCBI

6 

Gordon S: Alternative activation of macrophages. Nat Rev Immunol. 3:23–35. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Hai T and Hartman MG: The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: Activating transcription factor proteins and homeostasis. Gene. 273:1–11. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Hai T, Wolfgang CD, Marsee DK, Allen AE and Sivaprasad U: ATF3 and stress responses. Gene Expr. 7:321–335. 1999.PubMed/NCBI

9 

Thompson MR, Xu D and Williams BR: ATF3 transcription factor and its emerging roles in immunity and cancer. J Mol Med (Berl). 87:1053–1060. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Tsujino H, Kondo E, Fukuoka T, Dai Y, Tokunaga A, Miki K, Yonenobu K, Ochi T and Noguchi K: Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury. Mol Cell Neurosci. 15:170–182. 2000. View Article : Google Scholar : PubMed/NCBI

11 

Averill S, Michael GJ, Shortland PJ, Leavesley RC, King VR, Bradbury EJ, McMahon SB and Priestley JV: NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury. Eur J Neurosci. 19:1437–1445. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Nobori K, Ito H, Tamamori-Adachi M, Adachi S, Ono Y, Kawauchi J, Kitajima S, Marumo F and Isobe M: ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: A novel cardioprotective role of ATF3. J Mol Cell Cardiol. 34:1387–1397. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Yoshida T, Sugiura H, Mitobe M, Tsuchiya K, Shirota S, Nishimura S, Shiohira S, Ito H, Nobori K, Gullans SR, et al: ATF3 protects against renal ischemia-reperfusion injury. J Am Soc Nephrol. 19:217–224. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Nguyen CT, Kim EH, Luong TT, Pyo S and Rhee DK: TLR4 mediates pneumolysin-induced ATF3 expression through the JNK/p38 pathway in Streptococcus pneumoniae-infected RAW 264.7 cells. Mol Cells. 38:58–64. 2015.PubMed/NCBI

15 

Labzin LI, Schmidt SV, Masters SL, Beyer M, Krebs W, Klee K, Stahl R, Lütjohann D, Schultze JL, Latz E and De Nardo D: ATF3 is a key regulator of macrophage IFN responses. J Immunol. 195:4446–4455. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Lighvani S, Baik N, Diggs JE, Khaldoyanidi S, Parmer RJ and Miles LA: Regulation of macrophage migration by a novel plasminogen receptor Plg-R KT. Blood. 118:5622–5630. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Kim JS, Yeo S, Shin DG, Bae YS, Lee JJ, Chin BR, Lee CH and Baek SH: Glycogen synthase kinase 3beta and beta-catenin pathway is involved in toll-like receptor 4-mediated NADPH oxidase 1 expression in macrophages. FEBS J. 277:2830–2837. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Kraus C, Liehr T, Hülsken J, Behrens J, Birchmeier W, Grzeschik KH and Ballhausen WG: Localization of the human beta-catenin gene (CTNNB1) to 3p21: A region implicated in tumor development. Genomics. 23:272–274. 1994. View Article : Google Scholar : PubMed/NCBI

20 

Pedersen EA, Scannell CA, Menon R and Lawlor ER: Tenascin C is a canonical Wnt target gene in Ewing sarcoma and its expression is potentiated by R-spondin. Cancer Res. 74:3085. 2014. View Article : Google Scholar

21 

Kimura T, Tajiri K, Hlroe M, et al: Tenascin-C regulates macrophage behavior during tissue repair after myocardial infarction in mouse model. Molecular Biology Of The CellAmer Soc Cell Biology. Bethesda, MD: pp. 20814–2755. 2014

22 

Shimojo N, Hashizume R, Kanayama K, Hara M, Suzuki Y, Nishioka T, Hiroe M, Yoshida T and Imanaka-Yoshida K: Tenascin-C may accelerate cardiac fibrosis by activating macrophages via the integrin αVβ3/nuclear factor-κB/interleukin-6 axis. Hypertension. 66:757–766. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Mantovani A, Biswas SK, Galdiero MR, Sica A and Locati M: Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol. 229:176–185. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Gilchrist M, Thorsson V, Li B, Rust AG, Korb M, Roach JC, Kennedy K, Hai T, Bolouri H and Aderem A: Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature. 441:173–178. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Hai T, Wolford CC and Chang YS: ATF3, a hub of the cellular adaptive-response network, in the pathogenesis of diseases: Is modulation of inflammation a unifying component? Gene Expr. 15:1–11. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Chen HH, Lai PF, Lan YF, Cheng CF, Zhong WB, Lin YF, Chen TW and Lin H: Exosomal ATF3 RNA attenuates pro-inflammatory gene MCP-1 transcription in renal ischemia-reperfusion. J Cell Physiol. 229:1202–1211. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Zmuda EJ, Qi L, Zhu MX, Mirmira RG, Montminy MR and Hai T: The roles of ATF3, an adaptive-response gene, in high-fat-diet-induced diabetes and pancreatic beta-cell dysfunction. Mol Endocrinol. 24:1423–1433. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Li HF, Cheng CF, Liao WJ, Lin H and Yang RB: ATF3-mediated epigenetic regulation protects against acute kidney injury. J Am Soc Nephrol. 21:1003–1013. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Shan Y, Akram A, Amatullah H, Zhou DY, Gali PL, Maron-Gutierrez T, González-López A, Zhou L, Rocco PR, Hwang D, et al: ATF3 protects pulmonary resident cells from acute and ventilator-induced lung injury by preventing Nrf2 degradation. Antioxid Redox Signal. 22:651–668. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Murray PJ and Wynn TA: Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 11:723–737. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Yan L, Della Coletta L, Powell KL, Shen J, Thames H, Aldaz CM and MacLeod MC: Activation of the canonical Wnt/β-catenin pathway in ATF3-induced mammary tumors. PLoS One. 6:e165152011. View Article : Google Scholar : PubMed/NCBI

32 

Lee H, Bae S, Choi BW and Yoon Y: WNT/β-catenin pathway is modulated in asthma patients and LPS-stimulated RAW264.7 macrophage cell line. Immunopharmacol Immunotoxicol. 34:56–65. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Carey WA, Taylor GD, Dean WB and Bristow JD: Tenascin-C deficiency attenuates TGF-ß-mediated fibrosis following murine lung injury. Am J Physiol Lung Cell Mol Physiol. 299:L785–L793. 2010. View Article : Google Scholar : PubMed/NCBI

34 

Midwood K, Sacre S, Piccinini AM, Inglis J, Trebaul A, Chan E, Drexler S, Sofat N, Kashiwagi M, Orend G, et al: Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nature Med. 15:774–780. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Shimojo N, Hashizume R, Kanayama K, Suzuki Y, Hara M, Nishioka T, Yoshida T and Yoshida KI: A functional role of tenascin-C in angiotensin II-induced cardiac fibrosis. Circulation. 130:A96322014.

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Copy and paste a formatted citation
Spandidos Publications style
Sha H, Zhang D, Zhang Y, Wen Y and Wang Y: ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway. Mol Med Rep 16: 3641-3647, 2017.
APA
Sha, H., Zhang, D., Zhang, Y., Wen, Y., & Wang, Y. (2017). ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway. Molecular Medicine Reports, 16, 3641-3647. https://doi.org/10.3892/mmr.2017.6992
MLA
Sha, H., Zhang, D., Zhang, Y., Wen, Y., Wang, Y."ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway". Molecular Medicine Reports 16.3 (2017): 3641-3647.
Chicago
Sha, H., Zhang, D., Zhang, Y., Wen, Y., Wang, Y."ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway". Molecular Medicine Reports 16, no. 3 (2017): 3641-3647. https://doi.org/10.3892/mmr.2017.6992
Copy and paste a formatted citation
x
Spandidos Publications style
Sha H, Zhang D, Zhang Y, Wen Y and Wang Y: ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway. Mol Med Rep 16: 3641-3647, 2017.
APA
Sha, H., Zhang, D., Zhang, Y., Wen, Y., & Wang, Y. (2017). ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway. Molecular Medicine Reports, 16, 3641-3647. https://doi.org/10.3892/mmr.2017.6992
MLA
Sha, H., Zhang, D., Zhang, Y., Wen, Y., Wang, Y."ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway". Molecular Medicine Reports 16.3 (2017): 3641-3647.
Chicago
Sha, H., Zhang, D., Zhang, Y., Wen, Y., Wang, Y."ATF3 promotes migration and M1/M2 polarization of macrophages by activating tenascin‑C via Wnt/β‑catenin pathway". Molecular Medicine Reports 16, no. 3 (2017): 3641-3647. https://doi.org/10.3892/mmr.2017.6992
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