Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
October-2015 Volume 10 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
October-2015 Volume 10 Issue 4

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs

  • Authors:
    • Haiying Yue
    • Kai Hu
    • Wenqi Liu
    • Jie Jiang
    • Yuhua Chen
    • Rensheng Wang
  • View Affiliations / Copyright

    Affiliations: Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China, Department of Pathology, Guangxi Province Maternity and Child Care Hospital, Nanning, Guangxi 530002, P.R. China
  • Pages: 1437-1444
    |
    Published online on: July 27, 2015
       https://doi.org/10.3892/etm.2015.2658
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Radiation-induced lung injury (RILI) is a common complication associated with thoracic radiotherapy. The aim of the present study was to investigate the effects of a single 15-Gy dose of right-thoracic lung irradiation on the expression levels of matrix metalloproteinases (MMPs) and other proteins in the alveolar epithelial type II (AE2) cells of Bama minipigs. All minipigs received either right‑thoracic irradiation or sham irradiation under anesthesia, and were sacrificed at 4, 8, 12 or 24 weeks after irradiation. Collagen deposition was measured using Masson's trichrome staining. Surfactant protein A (SP‑A), transforming growth factor β1 (TGFβ1), MMP2, MMP9, vimentin and E‑cadherin protein expression levels were evaluated using western blot analysis, and the MMP2 and MMP9 gelatinase activities were tested using gelatin zymography. SP‑A and α‑smooth muscle actin (α‑SMA) co‑localization was visualized using double immunofluorescence staining. At each time‑point following irradiation, a significant increase in TGFβ1, α‑SMA, MMP2, MMP9 and vimentin protein expression levels and MMP2 and MMP9 gelatinase activity were observed in the irradiated lungs compared with the sham‑irradiated controls. By contrast, SP‑A and E‑cadherin protein expression levels decreased in a time‑dependent manner post‑irradiation. SP‑A and α‑SMA co‑localization was observed in irradiated alveolar epithelial cells. These data demonstrate that E‑cadherin, SP‑A, MMP2 and MMP9 may function as sensitive predictors of RILI. Epithelial‑mesenchymal transition (EMT) occurs in the irradiated lungs of Bama minipigs, and MMP2 and MMP9 may contribute to EMT in AE2 cells by regulating TGFβ1. Therefore, EMT may serve a crucial function in the development of RILI.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Stone HB, Coleman CN, Anscher MS and McBride WH: Effects of radiation on normal tissue: Consequences and mechanisms. Lancet Oncol. 4:529–536. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Cappuccini F, Eldh T, Bruder D, Gereke M, Jastrow H, SchulzeOsthoff K, Fischer U, Köhler D, Stuschke M and Jendrossek V: New insights into the molecular pathology of radiation-induced pneumopathy. Radiother Oncol. 101:86–92. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Trott KR, Herrmann T and Kasper M: Target cells in raditation pneumopathy. Int J Radiat Oncol Biol Phys. 58:463–469. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, Sheppard D and Chapman HA: Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA. 103:13180–13185. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Willis BC, Liebler JM, LubyPhelps K, Nicholson AG, Crandall ED, du Bois RM and Borok Z: Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1: Potential role in idiopathic pulmonary fibrosis. Am J Pathol. 166:1321–1332. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Almeida C, Nagarajan D, Tian J, Leal SW, Wheeler K, Munley M, Blackstock W and Zhao W: The role of alveolar epithelium in radiation-induced lung injury. PLoS One. 8:e536282013. View Article : Google Scholar : PubMed/NCBI

8 

Williams JP, Brown SL, Georges GE, HauerJensen M, Hill RP, Huser AK, Kirsch DG, Macvittie TJ, Mason KA, Medhora MM, et al: Animal models for medical countermeasures to radiation exposure. Radiat Res. 173:557–578. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Hopewell JW, Rezvani M and Moustafa HF: The pig as a model for the study of radiation effects on the lung. Int J Radiat Biol. 76:447–452. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Li M, Abdollahi A, Gröne HJ, Lipson KE, Belka C and Huber PE: Late treatment with imatinib mesylate ameliorates radiation-induced lung fibrosis in a mouse model. Radiat Oncol. 4:662009. View Article : Google Scholar : PubMed/NCBI

11 

Molthen RC, Wu Q, Fish BL, Moulder JE, Jacobs ER and Medhora MM: Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril. Respirology. 17:1261–1268. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Travis EL: The sequence of histological changes in mouse lungs after single doses of x-rays. Int J Radiat Oncol Biol Phys. 6:345–347. 1980. View Article : Google Scholar : PubMed/NCBI

13 

Uhal BD: Cell cycle kinetics in the alveolar epithelium. Am J Physiol. 272:L1030–L1045. 1997.

14 

Alcorn JF and Wright JR: Surfactant protein A inhibits alveolar macrophage cytokine production by CD14-independent pathway. Am J Physiol Lung Cell Mol Physiol. 286:L129–L136. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Vazquez de Lara LG, Umstead TM, Davis SE and Phelps DS: Surfactant protein A increases matrix metalloproteinase-9 production by THP-1 cells. Am J Physiol Lung Cell Mol Physiol. 285:L899–L906. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Hallman M, Maasilta P, Kivisaari L and Mattson K: Changes in surfactant in bronchoalveolar lavage fluid after hemithorax irradiation in patients with mesothelioma. Am Rev Respir Dis. 141:998–1005. 1990. View Article : Google Scholar : PubMed/NCBI

17 

Sasaki R, Soejima T, Matsumoto A, Maruta T, Yamada K, Ota Y, Kawabe T, Nishimura H, Sakai E, Ejima Y, et al: Clinical significance of serum pulmonary surfactant proteins A and D for the early detection of radiation pneumonitis. Int J Radiat Oncol Biol Phys. 50:301–307. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Wynn TA: Cellular and molecular mechanisms of fibrosis. J Pathol. 214:199–210. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Wynn TA: Integrating mechanisms of pulmonary fibrosis. J Exp Med. 208:1339–1350. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Nagarajan D, Melo T, Deng Z, Almeida C and Zhao W: ERK/GSK3β/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition. Free Radic Biol Med. 52:983–992. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Verrecchia F and Mauviel A: Transforming growth factor-beta and fibrosis. World J Gastroenterol. 13:3056–3062. 2007.PubMed/NCBI

22 

Thannickal VJ, Toews GB, White ES, Lynch JP III and Martinez FJ: Mechanisms of pulmonary fibrosis. Annu Rev Med. 55:395–417. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Zhao L, Sheldon K, Chen M, Yin MS, Hayman JA, Kalemkerian GP, Arenberg D, Lyons SE, Curtis JL, Davis M, et al: The predictive role of plasma TGF-β1 during radiation therapy for radiation-induced lung toxicity deserves further study in patients with non-small cell lung cancer. Lung Cancer. 59:232–239. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Visse R and Nagase H: Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry. Circ Res. 92:827–839. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Atkinson JJ and Senior RM: Matrix metalloproteinase-9 in lung remodeling. Am J Respir Cell Mol Biol. 28:12–24. 2003. View Article : Google Scholar : PubMed/NCBI

26 

López-Novoa JM and Nieto MA: Inflammation and EMT: An alliance towards organ fibrosis and cancer progression. EMBO Mol Med. 1:303–314. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Tan TK, Zheng G, Hsu TT, Wang Y, Lee VW, Tian X, Wang Y, Cao Q, Wang Y and Harris DC: Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells. Am J Pathol. 176:1256–1270. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Cheng S and Lovett DH: Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol. 162:1937–1949. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Lee WH, Warrington JP, Sonntag WE and Lee YW: Irradiation alters MMP-2/TIMP-2 system and collagen type IV degradation in brain. Int J Radiat Oncol Biol Phys. 82:1559–1566. 2012. View Article : Google Scholar : PubMed/NCBI

30 

StrupPerrot C, Vozenin-Brotons M-C, Vandamme M, Linard C and Mathé D: Expression of matrix metalloproteinases and tissue inhibitor metalloproteinases increases in X-irradiated rat ileum despite the disappearance of CD8a T cells. World J Gastroenterol. 11:6312–6321. 2005.PubMed/NCBI

31 

Yang K, Palm J, König J, Seeland U, Rosenkranz S, Feiden W, Rübe C and Rübe CE: Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury. Int J Radiat Biol. 83:665–676. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Susskind H, Hymowitz MH, Lau YH, Atkins HL, Hurewitz AN, Valentine ES, Meek AG and Zucker S: Increased plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer are altered during chest radiotherapy. Int J Radiat Oncol Biol Phys. 56:1161–1169. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Daley WP, Peters SB and Larsen M: Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci. 121:255–264. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Shintani Y, Maeda M, Chaika N, Johnson KR and Wheelock MJ: Collagen I promotes epithelial-to-mesenchymal transition in lung cancer cells via transforming growth factor-β signaling. Am J Respir Cell Mol Biol. 38:95–104. 2008. View Article : Google Scholar : PubMed/NCBI

35 

Zeisberg M, Bonner G, Maeshima Y, et al: Renal fibrosis: Collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation. Am J Pathol. 159:1313–1321. 2001. View Article : Google Scholar : PubMed/NCBI

36 

Buckley ST, Medina C, Davies AM and Ehrhardt C: Cytoskeletal re-arrangement in TGF-β1-induced alveolar epithelial-mesenchymal transition studied by atomic force microscopy and high-content analysis. Nanomedicine (Lond). 8:355–364. 2012.

37 

Kolb M, Margetts PJ, Sime PJ and Gauldie J: Proteoglycans decorin and biglycan differentially modulate TGF-beta-mediated fibrotic responses in the lung. Am J Physiol Lung Cell Mol Physiol. 280:L1327–L1334. 2001.PubMed/NCBI

38 

Kasai H, Allen JT, Mason RM, Kamimura T and Zhang Z: TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT). Respir Res. 6:562005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Yue H, Hu K, Liu W, Jiang J, Chen Y and Wang R: Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs. Exp Ther Med 10: 1437-1444, 2015.
APA
Yue, H., Hu, K., Liu, W., Jiang, J., Chen, Y., & Wang, R. (2015). Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs. Experimental and Therapeutic Medicine, 10, 1437-1444. https://doi.org/10.3892/etm.2015.2658
MLA
Yue, H., Hu, K., Liu, W., Jiang, J., Chen, Y., Wang, R."Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs". Experimental and Therapeutic Medicine 10.4 (2015): 1437-1444.
Chicago
Yue, H., Hu, K., Liu, W., Jiang, J., Chen, Y., Wang, R."Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs". Experimental and Therapeutic Medicine 10, no. 4 (2015): 1437-1444. https://doi.org/10.3892/etm.2015.2658
Copy and paste a formatted citation
x
Spandidos Publications style
Yue H, Hu K, Liu W, Jiang J, Chen Y and Wang R: Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs. Exp Ther Med 10: 1437-1444, 2015.
APA
Yue, H., Hu, K., Liu, W., Jiang, J., Chen, Y., & Wang, R. (2015). Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs. Experimental and Therapeutic Medicine, 10, 1437-1444. https://doi.org/10.3892/etm.2015.2658
MLA
Yue, H., Hu, K., Liu, W., Jiang, J., Chen, Y., Wang, R."Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs". Experimental and Therapeutic Medicine 10.4 (2015): 1437-1444.
Chicago
Yue, H., Hu, K., Liu, W., Jiang, J., Chen, Y., Wang, R."Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs". Experimental and Therapeutic Medicine 10, no. 4 (2015): 1437-1444. https://doi.org/10.3892/etm.2015.2658
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team