跳至主要内容

The Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Idiopathic Interstitisal Pneumoni

Read full paper at:
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=48647#.VK4VmcnQrzE

Background: Idiopathic interstitial pneumonia is characterized by fibroblast proliferation and extracellular matrix (ECM) accumulation. Matrix metalloproteases (MMPs) and tissue inhibitors of metalloproteases (TIMPs) have been shown to regulate remodeling of the ECM, which indicates that they are important factors in the process of lung fibrosis. Therefore, we evaluated the expression of MMPs and TIMPs in tissues obtained from patients with idiopathic interstitial pneumonia and control tissues. Methods: Thirty-seven patients who were diagnosed with IIP (22: IPF, 13: NSIP, 2: COP) and 5 controls were enrolled in this study. The MMP-2 and -9 activity in lung tissue obtained from these patients was analyzed using gelatin zymography and the levels of TIMP-1 and -2 were measured by western blotting. We also evaluated the expression of MMP-2 and -9, as well as that of TIMP-1 and -2 in lung tissue using immunohistochemistry. Results: The levels of MMP-2 and MMP-9 were significantly increased in patients with IPF compared to those with NSIP and COP. The activities of TIMP-1 and -2 were also higher in patients with IPF than NSIP/COP patients and control subjects. There were no significant differences observed in the activities of MMPs and TIMPs obtained from patients with NSIP/COP and control subjects. The immunohistochemical analysis showed that TIMP-2 and MMP-2 were strongly stained at the fibroblasts of the fibroblastic foci in patients with IPF. Conclusions: These results suggest that over-expression of gelatinases and TIMPs in patients with IPF are important factors in the irreversible fibrosis that is associated with lung parenchyma.
Cite this paper
Shin, J. , Kim, Y. , Kyung, S. , Ha, S. and Jeong, S. (2014) The Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Idiopathic Interstitisal Pneumonia. Open Journal of Respiratory Diseases, 4, 101-109. doi: 10.4236/ojrd.2014.43014.
 

[1] American Thoracic Society (2002) American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. American Journal of Respiratory and Critical Care Medicine, 165, 277-304.
[2] Gross, T.J. and Hunninhake, G.W. (2001) Idiopathic Pulmonary Fibrosis. New England Journal of Medicine, 345, 517-525.
http://dx.doi.org/10.1056/NEJMra003200
[3] King Jr., T.E. (2003) Idiopathic Interstitial Pneumonia. In: Schwarz, M.I. and King Jr., T.E., Eds., Interstitial Lung Disease, BC Decker Inc., London, 701-786.
[4] Katzenstein, A.L. and Fiorelli, R.F. (1994) Nonspecific Interstitial Pneumonia/Fibrosis; Histologic Features and Clinical Significance. American Journal of Surgical Pathology, 18, 136-147.
http://dx.doi.org/10.1097/00000478-199402000-00003
[5] Epler, G.R., Colby, T.V., McLoud, T.C., et al. (1985) Bronchiolitis Obliterans Organizing Pneumonia. New England Journal of Medicine, 312, 152-158.
http://dx.doi.org/10.1056/NEJM198501173120304
[6] Selman, M., Ruiz, V., Cabrea, S., et al. (2000) TIMP-1, -2, -3, and -4 in Idiopathic Pulmonary Fibrosis. A Prevailing Nondegradative Lung Microenvironment? American Journal of Physiology-Lung Cellular and Molecular Physiology, 279, L562-L574.
[7] Murphy, G. and Docherty, A.J. (2003) The Matrix Metalloproteinases and Their Inhibitors. American Journal of Medicine, 65, 196-204.
[8] Atkinson, J.J. and Senior, R.M. (2003) Matrix Metalloproteinase-9 in Lung Remodeling. American Journal of Respiratory Cell and Molecular Biology, 28, 12-24.
http://dx.doi.org/10.1165/rcmb.2002-0166TR
[9] Sternlicht, M.D. and Werb, Z. (2001) How Matrix Metalloproteases Regulate Cell Behavior. Annual Review of Cell and Developmental Biology, 17, 463-516.
http://dx.doi.org/10.1146/annurev.cellbio.17.1.463
[10] Fukuda, Y., Ishizake, M., Kudoh, S., et al. (1998) Localization of Matrix Metalloproteinases-1, -2, and -9, and Tissue Inhibitor of Metalloproteinase-2 in Interstitial Lung Diseases. Laboratory Investigation, 78, 687-698.
[11] Lamjabbar, H., Gosset, P., Lechapt-Zalcman, E., Franco-Montoya, M.L., Wallaert, B., Harf, A., et al. (1999) Overexpression of Alveolar Macrophage Gelatinase B (MMP-9) in Patients with Idiopathic Pulmonary Fibrosis: Effects of Steroid and Immunosuppressive Treatment. American Journal of Respiratory Cell and Molecular Biology, 20, 903-913.
http://dx.doi.org/10.1165/ajrcmb.20.5.3260
[12] Suga, M., Iyonaga, K., Okamoto, T., Gushima, Y., Miyakawa, H., Akaike, T., et al. (2000) Characteristic Elevation of Matrix Metalloproteinase Activity in Idiopathic Interstitial Pneumonias. American Journal of Respiratory Cell and Critical Care Medicine, 162, 1949-1956.
http://dx.doi.org/10.1164/ajrccm.162.5.9906096
[13] Pardo, A. and Selman, M. (2006) Matrix Metalloproteases in Aberrant Fibrotic Tissue Remodeling. Proceedings of the American Thoracic Society, 3, 383-388.
http://dx.doi.org/10.1513/pats.200601-012TK
[14] Choi, K.H., Lee, H., Jeong, M.Y., Rhee, Y.K., Chung, M.J., Kwak, Y.G., et al. (2002) The Role of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Cryptogenic Organizing Pneumonia. Chest, 121, 1478-1485.
http://dx.doi.org/10.1378/chest.121.5.1478
[15] Hayashi, T., Stetler-Stevenson, W.G., Fleming, M.V., Fishback, N., Koss, M.N., Liotta, L.A., et al. (1996) Immunohistochemical Study of Metalloproteinases and Their Tissue Inhibitors in the Lungs of Patients with Diffuse Alveolar Damage and Idiopathic Pulmonary Fibrosis. American Journal of Pathology, 149, 1241-1256.
[16] Selman, M., King Jr., T.E. and Pardo, A. (2001) Idiopathic Pulmonary Fibrosis: Prevailing and Evolving Hypotheses about Its Pathogenesis and Implications for Therapy. Annals of Internal Medicine, 134, 136-151.
http://dx.doi.org/10.7326/0003-4819-134-2-200101160-00015
[17] Okuda, S., Kita, H., George, T.J., Gleich, G.J. and Leiferman, K.M. (1997) Migration of Eosinophils through Basement Membrane Components in Vitro: Role of Metrix Metalloprotease-9. American Journal of Respiratory Cell and Molecular Biology, 17, 519-528.
http://dx.doi.org/10.1165/ajrcmb.17.4.2877
[18] Madtes, D.K., Eliston, A.L., Kaback, L.A. and Clark, J.G. (2001) Selective Induction of Tissue Inhibitor of Metalloproteinase-1 in Bleomycin-Induced Pulmonary Fibrosis. American Journal of Respiratory Cell and Molecular Biology, 24, 599-607.
http://dx.doi.org/10.1165/ajrcmb.24.5.4192
[19] Pardo, A., Selman, M., Ramaarez, R., Ramos, C., Stricklin, G., Raghu, G., et al. (1992) Production of Collagenase and Tissue Inhibitor of Metalloproteases by Fibroblasts Derived from Normal and Fibrotic Human Lung. Chest, 102, 1085-1089.
http://dx.doi.org/10.1378/chest.102.4.1085
[20] King Jr., T.E., Schwarz, M.I., Brown, K., Tooze, J.A., Colby, T.V., Waldron Jr., J.A., et al. (2001) Idiopathic Pulmonary Fibrosis. Relationship between Histopathologic Features and Mortality. American Journal of Respiratory and Critical Care Medicine, 164, 1025-1032.
http://dx.doi.org/10.1164/ajrccm.164.6.2001056
[21] Sienel, W., Hellers, J., Morresihaul, A., Lichtinghagen, R., Mutschler, W., Jochum, M., et al. (2003) Prognostic Impact of Matrix Metalloproteinase-9 in Operable Non-Small Cell Lung Cancer. International Journal of Cancer, 103, 647-651.
http://dx.doi.org/10.1002/ijc.10841   eww150108lx

评论

此博客中的热门博文

Electron Spin and Proton Spin in the Hydrogen and Hydrogen-Like Atomic Systems

Read full paper at: http://www.scirp.org/journal/PaperInformation.aspx?PaperID=52202#.VIj7tMnQrzE Author(s) Stanisław Olszewski * Affiliation(s) Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland . ABSTRACT The mechanical angular momentum and magnetic moment of the electron and proton spin have been calculated semiclassically with the aid of the uncertainty principle for energy and time. The spin effects of both kinds of the elementary particles can be expressed in terms of similar formulae. The quantization of the spin motion has been done on the basis of the old quantum theory. It gives a quantum number n = 1/2 as the index of the spin state acceptable for both the electron and proton ...

A Study on the Seismic Isolation Systems of Bridges with Lead Rubber Bearings

Read full paper at: http://www.scirp.org/journal/PaperInformation.aspx?PaperID=52566#.VJt06cCAM4 Author(s)   Woo-Suk Kim , Dong-Joon Ahn , Jong-Kook Lee Affiliation(s) School of Architecture, Kumoh National Institute of Technology, Gumi, Republic of Korea . ABSTRACT This study consists of the development and presentation of example of seismic isolation system analysis and design for a continuous, 3-span, cast-in-place concrete box girder bridge. It is expected that example is developed for all Lead-Rubber Bearing (LRB) seismic isolation system on piers and abutments which placed in between super-structure and sub-structure. Design forces, displacements, and drifts are given distinctive consideration in...

Effects of Karate Training on Basic Motor Abilities of Primary School Children

“You never attack first in karate” might be the best conclusion of karate, which is a martial art practiced typically without weapons. It’s reported that karate has a long history for several hundred years, but the modern karate was spread to the whole Japan from Okinawa in the early part of 20th century. Now it has become one of the most widely practiced martial art forms in the world. Usually, it’s divided into Kihon, Kata and Kumite. As for the beginners, Kihon is more suitable for them because it involves basic techniques. Due to karate consists of dynamic offensive and defensive techniques using all parts of the body to their maximum advantage, the best understanding of true karate practice is the perfection of oneself through the perfection of the art. It not only develops coordination, quickens reflexes, and builds stamina, but also develops composure, a clearer thought process, deeper insight into one’s mental capabilities, and more self-confidence. So many researchers stu...