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The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity

  • Authors:
    • Fei Li
    • Xuefeng Xu
    • Jing Geng
    • Xuan Wan
    • Huaping Dai
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary and Critical Care Medicine, Beijing An‑Zhen Hospital, Capital Medical University, Beijing 100029, P.R. China, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China‑Japan Friendship Hospital, Capital Medical University, National Clinical Research Center for Respiratory Diseases, Beijing 100029, P.R. China, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1844-1854
    |
    Published online on: January 8, 2020
       https://doi.org/10.3892/etm.2020.8433
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Abstract

The C‑X‑C Motif Chemokine Receptor 4/C‑X‑C Motif Chemokine Ligand 12 (CXCR4/CXCL12) axis has been implicated in the pathogenesis of pulmonary fibrosis. However, the mechanisms governing this remain to be determined. The current study demonstrated that human lung fibroblasts (HLFs) exhibit high CXCL12 expression and also exhibit high expression of its corresponding receptor CXCR4. Exogenous CXCL12 was revealed to significantly promote the migration and proliferation of HLFs, and potentiate CXCR4 expression. These effects were demonstrated to be inhibited by AMD3100, which is an antagonist of CXCR4. Lung and bronchoalveolar lavage fluid CXCR4 and CXCL12 expression was upregulated by in vivo bleomycin administration, which was partially inhibited by pre‑treatment with AMD3100. AMD3100 also reduced lung collagen content in the bleomycin model. Inhibiting CXCR4 was indicated to ameliorate the lung compliance and resistance of pulmonary fibrosis. In conclusion, the results of the present study suggested that autocrine CXCR4/CXCL12 axis is an important mechanism underlying the pathogenesis of idiopathic pulmonary fibrosis, and may serve as a potential therapeutic target that can be used in the treatment of pulmonary disease.
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1 

Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, et al: Diagnosis of idiopathic pulmonary fibrosis. An official ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med. 198:e44–e68. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Richeldi L, Collard HR and Jones MG: Idiopathic pulmonary fibrosis. Lancet. 389:1941–1952. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Wolters PJ, Collard HR and Jones KD: Pathogenesis of idiopathic pulmonary fibrosis. Annu Rev Pathol. 9:157–179. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Legler DF and Thelen M: Chemokines: Chemistry, biochemistry and biological function. Chimia (Aarau). 70:856–859. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Liekens S, Schols D and Hatse S: CXCL12-CXCR4 axis in angiogenesis, metastasis and stem cell mobilization. Curr Pharm Des. 16:3903–3920. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Li J, Li T, Li S, Xie L, Yang YL, Lin Q, Kadoch O, Li H, Hou S and Xu Z: Experimental study of the inhibition effect of CXCL12/CXCR4 in malignant pleural mesothelioma. J Investig Med. 67:338–345. 2019. View Article : Google Scholar : PubMed/NCBI

7 

Miller RJ, Banisadr G and Bhattacharyya BJ: CXCR4 signaling in the regulation of stem cell migration and development. J Neuroimmunol. 198:31–38. 2008. View Article : Google Scholar : PubMed/NCBI

8 

He W, Yang T, Gong XH, Qin RZ, Zhang XD and Liu WD: Targeting CXC motif chemokine receptor 4 inhibits the proliferation, migration and angiogenesis of lung cancer cells. Oncol Lett. 16:3976–3982. 2018.PubMed/NCBI

9 

Bagnato G and Harari S: Cellular interactions in the pathogenesis of interstitial lung diseases. Eur Respir Rev. 24:102–114. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY, Belperio JA, Keane MP and Strieter RM: Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest. 114:438–446. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Mehrad B, Burdick MD and Strieter RM: Fibrocyte CXCR4 regulation as a therapeutic target in pulmonary fibrosis. Int J Biochem Cell Biol. 41:1708–1718. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Xu J, Mora A, Shim H, Stecenko A, Brigham KL and Rojas M: Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and fibrosis. Am J Respir Cell Mol Biol. 37:291–299. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Makino H, Aono Y, Azuma M, Kishi M, Yokota Y, Kinoshita K, Takezaki A, Kishi J, Kawano H, Ogawa H, et al: Antifibrotic effects of CXCR4 antagonist in bleomycin-induced pulmonary fibrosis in mice. J Med Invest. 60:127–137. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Kleaveland KR, Velikoff M, Yang J, Agarwal M, Rippe RA, Moore BB and Kim KK: Fibrocytes are not an essential source of type I collagen during lung fibrosis. J Immunol. 193:5229–5239. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Barbero S, Bonavia R, Bajetto A, Porcile C, Pirani P, Ravetti JL, Zona GL, Spaziante R, Florio T and Schettini G: Stromal cell-derived factor 1alpha stimulates human glioblastoma cell growth through the activation of both extracellular signal-regulated kinases 1/2 and Akt. Cancer Res. 63:1969–1974. 2003.PubMed/NCBI

16 

Wang X, Cao Y, Zhang S, Chen Z, Fan L, Shen X, Zhou S and Chen D: Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer. Oncotarget. 8:36149–36160. 2017.PubMed/NCBI

17 

Guo S, Xiao D, Liu H, Zheng X, Liu L and Liu S: Interfering with CXCR4 expression inhibits proliferation, adhesion and migration of breast cancer MDA-MB-231 cells. Oncol Lett. 8:1557–1562. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Abraham M, Klein S, Bulvik B, Wald H, Weiss ID, Olam D, Weiss L, Beider K, Eizenberg O, Wald O, et al: The CXCR4 inhibitor BL-8040 induces the apoptosis of AML blasts by downregulating ERK, BCL-2, MCL-1 and cyclin-D1 via altered miR-15a/16-1 expression. Leukemia. 31:2336–2346. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Xu X, Wan X, Geng J, Li F, Wang C and Dai H: Kinase inhibitors fail to induce mesenchymal-epithelial transition in fibroblasts from fibrotic lung tissue. Int J Mol Med. 32:430–438. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Huang J, Li Z, Yao X, Li Y, Reng X, Li J, Wang W, Gao J, Wang C, Tankersley CG and Huang K: Altered Th1/Th2 commitment contributes to lung senescence in CXCR3-deficient mice. Exp Gerontol. 48:717–726. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Ashcroft T, Simpson JM and Timbrell V: Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 41:467–470. 1988. View Article : Google Scholar : PubMed/NCBI

22 

Shimizu Y, Dobashi K, Endou K, Ono A, Yanagitani N, Utsugi M, Sano T, Ishizuka T, Shimizu K, Tanaka S and Mori M: Decreased interstitial FOXP3(+) lymphocytes in usual interstitial pneumonia with discrepancy of CXCL12/CXCR4 axis. Int J Immunopathol Pharmacol. 23:449–461. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Buck AK, Stolzenburg A, Hänscheid H, Schirbel A, Lückerath K, Schottelius M, Wester HJ and Lapa C: Chemokine receptor-directed imaging and therapy. Methods. 130:63–71. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Balkwill F: Chemokine biology in cancer. Semin Immunol. 15:49–55. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Balkwill F: The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol. 14:171–179. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Dai Z, Li M, Wharton J, Zhu MM and Zhao YY: Prolyl-4 Hydroxylase 2 (PHD2) deficiency in endothelial cells and hematopoietic cells induces obliterative vascular remodeling and severe pulmonary arterial hypertension in mice and humans through hypoxia-inducible factor-2α. Circulation. 133:2447–2458. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Dai Z, Zhu MM, Peng Y, Jin H, Machireddy N, Qian Z, Zhang X and Zhao YY: Endothelial and smooth muscle cell interaction via FoxM1 signaling mediates vascular remodeling and pulmonary hypertension. Am J Respir Crit Care Med. 198:788–802. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Andersson-Sjöland A, de Alba CG, Nihlberg K, Becerril C, Ramírez R, Pardo A, Westergren-Thorsson G and Selman M: Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis. Int J Biochem Cell Biol. 40:2129–2140. 2008. View Article : Google Scholar : PubMed/NCBI

29 

Mehrad B, Burdick MD, Zisman DA, Keane MP, Belperio JA and Strieter RM: Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease. Biochem Biophys Res Commun. 353:104–108. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Lin CH, Shih CH, Tseng CC, Yu CC, Tsai YJ, Bien MY and Chen BC: CXCL12 induces connective tissue growth factor expression in human lung fibroblasts through the Rac1/ERK, JNK, and AP-1 pathways. PLoS One. 9:e1047462014. View Article : Google Scholar : PubMed/NCBI

31 

Tian Y, Yin H, Deng X, Tang B, Ren X and Jiang T: CXCL12 induces migration of oligodendrocyte precursor cells through the CXCR4-activated MEK/ERK and PI3K/AKT pathways. Mol Med Rep. 18:4374–4380. 2018.PubMed/NCBI

32 

Penke LR, Speth JM, Dommeti VL, White ES, Bergin IL and Peters-Golden M: FOXM1 is a critical driver of lung fibroblast activation and fibrogenesis. J Clin Invest. 128:2389–2405. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Rock JR, Barkauskas CE, Cronce MJ, Xue Y, Harris JR, Liang J, Noble PW and Hogan BL: Multiple stromal populations contribute to pulmonary fibrosiswithout evidence for epithelial to mesenchymal transition. Proc Natl Acad Sci USA. 108:E1475–E1483. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Xie T, Liang J, Liu N, Huan C, Zhang Y, Liu W, Kumar M, Xiao R, D'Armiento J, Metzger D, et al: Transcription factor TBX4 regulates myofibroblast accumulation and lung fibrosis. J Clin Invest. 126:3063–3079. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li F, Xu X, Geng J, Wan X and Dai H: The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity. Exp Ther Med 19: 1844-1854, 2020.
APA
Li, F., Xu, X., Geng, J., Wan, X., & Dai, H. (2020). The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity. Experimental and Therapeutic Medicine, 19, 1844-1854. https://doi.org/10.3892/etm.2020.8433
MLA
Li, F., Xu, X., Geng, J., Wan, X., Dai, H."The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity". Experimental and Therapeutic Medicine 19.3 (2020): 1844-1854.
Chicago
Li, F., Xu, X., Geng, J., Wan, X., Dai, H."The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity". Experimental and Therapeutic Medicine 19, no. 3 (2020): 1844-1854. https://doi.org/10.3892/etm.2020.8433
Copy and paste a formatted citation
x
Spandidos Publications style
Li F, Xu X, Geng J, Wan X and Dai H: The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity. Exp Ther Med 19: 1844-1854, 2020.
APA
Li, F., Xu, X., Geng, J., Wan, X., & Dai, H. (2020). The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity. Experimental and Therapeutic Medicine, 19, 1844-1854. https://doi.org/10.3892/etm.2020.8433
MLA
Li, F., Xu, X., Geng, J., Wan, X., Dai, H."The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity". Experimental and Therapeutic Medicine 19.3 (2020): 1844-1854.
Chicago
Li, F., Xu, X., Geng, J., Wan, X., Dai, H."The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity". Experimental and Therapeutic Medicine 19, no. 3 (2020): 1844-1854. https://doi.org/10.3892/etm.2020.8433
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