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Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury.
Int J Radiat Biol. 2007 Oct; 83(10):665-76.IJ

Abstract

PURPOSE

Remodeling of extracellular matrix (ECM) after lung damage depends on collagen degrading Matrix-Metallo-Proteinases (MMP) and their endogenous inhibitors (Tissue-Inhibitors of Metallo-Proteinases, TIMP). Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of radiation-induced lung fibrosis upon its effects on fibroblast proliferation and collagen synthesis. Lung cancer patients have often elevated TGF-beta1 plasma levels as a result of increased TGF-beta1 expression in their tumours. On this background, we investigated the effect of irradiation on the MMP/TIMP system in the lung tissue of normal and transgenic TGF-beta1 mice, in which TGF-beta1 is overexpressed in the liver resulting in high TGF-beta1 plasma levels.

MATERIAL AND METHODS

Transgenic (TG) and wild-type (WT) mice underwent thoracic irradiation with 12 Gy or sham-irradiation. For each study group (TG 12 Gy; TG 0 Gy; WT 12 Gy; WT 0 Gy) 8 mice were sacrificed at 4 and 8 weeks after (sham-) irradiation. The TGF-beta1, TIMP-1/-2/-3 expression in the lung tissue was quantified by Western blot; the MMP-2 and MMP-9 activity was analysed by zymography. The cellular origin of the MMP and TIMP was localised by immunohistochemistry.

RESULTS

Irradiation had no influence on the TIMP-1/-2/-3, but increased significantly the MMP-2 /-9 expression. In the lung tissue of TG mice the TIMP-1/-2/-3 expression was elevated, the MMP-9 activity was decreased. The immunhistochemical study showed that parenchymal and inflammatory cells express these MMP/TIMP.

CONCLUSION

Our results provide evidence that the overexpression of MMP-2 and MMP-9 is involved in the inflammatory response of radiation-induced lung injury. MMP-2 and MMP-9 are known to degrade collagen IV of basement membranes, therefore affecting the structural integrity of lung tissue. In contrast, in lung tissue of TG mice the TIMP-1/-2/-3 expression was up-regulated and the MMP-9 activity was diminished, thereby decreasing possibly the ECM degradation leading to lung fibrosis.

Authors+Show Affiliations

Department of Radiotherapy and Radiooncology, Saarland University, Homburg/Saar, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17729161

Citation

Yang, Kunyu, et al. "Matrix-Metallo-Proteinases and Their Tissue Inhibitors in Radiation-induced Lung Injury." International Journal of Radiation Biology, vol. 83, no. 10, 2007, pp. 665-76.
Yang K, Palm J, König J, et al. Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury. Int J Radiat Biol. 2007;83(10):665-76.
Yang, K., Palm, J., König, J., Seeland, U., Rosenkranz, S., Feiden, W., Rübe, C., & Rübe, C. E. (2007). Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury. International Journal of Radiation Biology, 83(10), 665-76.
Yang K, et al. Matrix-Metallo-Proteinases and Their Tissue Inhibitors in Radiation-induced Lung Injury. Int J Radiat Biol. 2007;83(10):665-76. PubMed PMID: 17729161.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Matrix-Metallo-Proteinases and their tissue inhibitors in radiation-induced lung injury. AU - Yang,Kunyu, AU - Palm,Jan, AU - König,Jochem, AU - Seeland,Ute, AU - Rosenkranz,Stephan, AU - Feiden,Wolfgang, AU - Rübe,Christian, AU - Rübe,Claudia E, PY - 2007/8/31/pubmed PY - 2008/1/5/medline PY - 2007/8/31/entrez SP - 665 EP - 76 JF - International journal of radiation biology JO - Int J Radiat Biol VL - 83 IS - 10 N2 - PURPOSE: Remodeling of extracellular matrix (ECM) after lung damage depends on collagen degrading Matrix-Metallo-Proteinases (MMP) and their endogenous inhibitors (Tissue-Inhibitors of Metallo-Proteinases, TIMP). Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of radiation-induced lung fibrosis upon its effects on fibroblast proliferation and collagen synthesis. Lung cancer patients have often elevated TGF-beta1 plasma levels as a result of increased TGF-beta1 expression in their tumours. On this background, we investigated the effect of irradiation on the MMP/TIMP system in the lung tissue of normal and transgenic TGF-beta1 mice, in which TGF-beta1 is overexpressed in the liver resulting in high TGF-beta1 plasma levels. MATERIAL AND METHODS: Transgenic (TG) and wild-type (WT) mice underwent thoracic irradiation with 12 Gy or sham-irradiation. For each study group (TG 12 Gy; TG 0 Gy; WT 12 Gy; WT 0 Gy) 8 mice were sacrificed at 4 and 8 weeks after (sham-) irradiation. The TGF-beta1, TIMP-1/-2/-3 expression in the lung tissue was quantified by Western blot; the MMP-2 and MMP-9 activity was analysed by zymography. The cellular origin of the MMP and TIMP was localised by immunohistochemistry. RESULTS: Irradiation had no influence on the TIMP-1/-2/-3, but increased significantly the MMP-2 /-9 expression. In the lung tissue of TG mice the TIMP-1/-2/-3 expression was elevated, the MMP-9 activity was decreased. The immunhistochemical study showed that parenchymal and inflammatory cells express these MMP/TIMP. CONCLUSION: Our results provide evidence that the overexpression of MMP-2 and MMP-9 is involved in the inflammatory response of radiation-induced lung injury. MMP-2 and MMP-9 are known to degrade collagen IV of basement membranes, therefore affecting the structural integrity of lung tissue. In contrast, in lung tissue of TG mice the TIMP-1/-2/-3 expression was up-regulated and the MMP-9 activity was diminished, thereby decreasing possibly the ECM degradation leading to lung fibrosis. SN - 0955-3002 UR - https://www.unboundmedicine.com/medline/citation/17729161/Matrix_Metallo_Proteinases_and_their_tissue_inhibitors_in_radiation_induced_lung_injury_ L2 - https://www.tandfonline.com/doi/full/10.1080/09553000701558977 DB - PRIME DP - Unbound Medicine ER -