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Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary fibrosis patients.

Park JS, Park HJ, Park YS, Lee SM, Yim JJ, Yoo CG, Han SK, Kim YW - BMC Pulm Med (2014)

Bottom Line: Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant.ROCK1 was not associated with the studied clinicopathological features.Further studies involving large numbers of homogeneous IPF patients are warranted.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. ywkim@snu.ac.kr.

ABSTRACT

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern.

Methods: The mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features.

Results: The mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features.

Conclusions: The mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.

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Representative lung tissue sections from healthy individuals and patients with usual interstitial pneumonia (UIP), stained for mTOR, ZEB1, and ROCK1. The mTOR, ZEB1 and ROCK1 expression was not detected in alveolar epithelial cells of control normal lung tissue (Figure 2A, E, I, immunohistochemical staining, brown color, 200× magnification). Staining was weak or absent in normal area of UIP lungs (Figure 2B, F, J, 400× magnification). Cells overlying fibroblastic foci showed weak staining, however mesenchymal cells of the fibroblastic foci did not show mTOR, ZEB1 and ROCK1 expression (Figure 2C, G, K; arrows denote location of fibroblastic focus, 400× magnification). Expression of mTOR, ZEB1 and ROCK1 was compared in same fibrotic area (Figure 2D, H, L, 400× magnification).
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Fig2: Representative lung tissue sections from healthy individuals and patients with usual interstitial pneumonia (UIP), stained for mTOR, ZEB1, and ROCK1. The mTOR, ZEB1 and ROCK1 expression was not detected in alveolar epithelial cells of control normal lung tissue (Figure 2A, E, I, immunohistochemical staining, brown color, 200× magnification). Staining was weak or absent in normal area of UIP lungs (Figure 2B, F, J, 400× magnification). Cells overlying fibroblastic foci showed weak staining, however mesenchymal cells of the fibroblastic foci did not show mTOR, ZEB1 and ROCK1 expression (Figure 2C, G, K; arrows denote location of fibroblastic focus, 400× magnification). Expression of mTOR, ZEB1 and ROCK1 was compared in same fibrotic area (Figure 2D, H, L, 400× magnification).

Mentions: The mTOR and ZEB1 were mainly expressed in the hyperplastic alveolar epithelial cells and in some mesenchymal cells of UIP lungs (Figure 1C,D,E,F). The ROCK1 expression was detected in the hyperplastic alveolar epithelial cells, some mesenchymal cells, macrophages, and lymphocytes of the UIP patients (Figure 1G,H). The mTOR, ZEB1 expression was not detected in the control normal lung tissue, except in the bronchial epithelial cells (Figure 2A, E). ROCK1 expression was not detected in the normal lung tissue alveolar epithelial cells, but detected in bronchial epithelial cells and surrounding smooth muscle cells (Figure 2I). Cells overlying fibroblastic foci showed weak staining, however mesenchymal cells of the fibroblastic foci did not show mTOR, ZEB1 and ROCK1 expression (Figure 2C, G, K). Staining was weak or absent in normal area of UIP lungs (Figure 2B, F, J).Figure 2


Clinical significance of mTOR, ZEB1, ROCK1 expression in lung tissues of pulmonary fibrosis patients.

Park JS, Park HJ, Park YS, Lee SM, Yim JJ, Yoo CG, Han SK, Kim YW - BMC Pulm Med (2014)

Representative lung tissue sections from healthy individuals and patients with usual interstitial pneumonia (UIP), stained for mTOR, ZEB1, and ROCK1. The mTOR, ZEB1 and ROCK1 expression was not detected in alveolar epithelial cells of control normal lung tissue (Figure 2A, E, I, immunohistochemical staining, brown color, 200× magnification). Staining was weak or absent in normal area of UIP lungs (Figure 2B, F, J, 400× magnification). Cells overlying fibroblastic foci showed weak staining, however mesenchymal cells of the fibroblastic foci did not show mTOR, ZEB1 and ROCK1 expression (Figure 2C, G, K; arrows denote location of fibroblastic focus, 400× magnification). Expression of mTOR, ZEB1 and ROCK1 was compared in same fibrotic area (Figure 2D, H, L, 400× magnification).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4233073&req=5

Fig2: Representative lung tissue sections from healthy individuals and patients with usual interstitial pneumonia (UIP), stained for mTOR, ZEB1, and ROCK1. The mTOR, ZEB1 and ROCK1 expression was not detected in alveolar epithelial cells of control normal lung tissue (Figure 2A, E, I, immunohistochemical staining, brown color, 200× magnification). Staining was weak or absent in normal area of UIP lungs (Figure 2B, F, J, 400× magnification). Cells overlying fibroblastic foci showed weak staining, however mesenchymal cells of the fibroblastic foci did not show mTOR, ZEB1 and ROCK1 expression (Figure 2C, G, K; arrows denote location of fibroblastic focus, 400× magnification). Expression of mTOR, ZEB1 and ROCK1 was compared in same fibrotic area (Figure 2D, H, L, 400× magnification).
Mentions: The mTOR and ZEB1 were mainly expressed in the hyperplastic alveolar epithelial cells and in some mesenchymal cells of UIP lungs (Figure 1C,D,E,F). The ROCK1 expression was detected in the hyperplastic alveolar epithelial cells, some mesenchymal cells, macrophages, and lymphocytes of the UIP patients (Figure 1G,H). The mTOR, ZEB1 expression was not detected in the control normal lung tissue, except in the bronchial epithelial cells (Figure 2A, E). ROCK1 expression was not detected in the normal lung tissue alveolar epithelial cells, but detected in bronchial epithelial cells and surrounding smooth muscle cells (Figure 2I). Cells overlying fibroblastic foci showed weak staining, however mesenchymal cells of the fibroblastic foci did not show mTOR, ZEB1 and ROCK1 expression (Figure 2C, G, K). Staining was weak or absent in normal area of UIP lungs (Figure 2B, F, J).Figure 2

Bottom Line: Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant.ROCK1 was not associated with the studied clinicopathological features.Further studies involving large numbers of homogeneous IPF patients are warranted.

View Article: PubMed Central - PubMed

Affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea. ywkim@snu.ac.kr.

ABSTRACT

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes. Three proteins (mammalian target of rapamycin, mTOR; zinc finger E-box-binding homeobox 1, ZEB1; Rho-associated, coiled-coil containing protein kinase 1, ROCK1) may be related to pulmonary fibrosis. However, they have not been assessed in human pulmonary fibrosis. We assessed the clinical significance of mTOR, ZEB1, and ROCK1 expression in human pulmonary fibrosis of usual interstitial pneumonia (UIP) pattern.

Methods: The mTOR, ZEB1, and ROCK1 expression was evaluated by immunohistochemical staining of 30 surgical lung biopsy tissues from 26 IPF and 4 UIP pattern connective tissue disease related interstitial lung disease (CTD-ILD) patients. The expression scores correlated with the clinical features.

Results: The mTOR, ZEB1 and ROCK1 mainly expressed in alveolar epithelial cells of UIP lungs. The histological fibrosis scores and lung function decline in the strong mTOR expression group were higher than those in the weak and intermediate expression group. Patients with positive ZEB1 expression had higher fibrosis scores and greater decline in carbon monoxide diffusion capacity (DLCO) than patients with negative ZEB1 expression. Patients with positive mTOR or ZEB1 expression had poorer prognosis than that of patients with negative mTOR or ZEB1 expression, although it was not statistically significant. ROCK1 was not associated with the studied clinicopathological features.

Conclusions: The mTOR and ZEB1 expression in pulmonary fibrosis patients significantly correlated with the fibrosis score and lung function decline, indicating that it may be related to the prognosis of pulmonary fibrosis. Further studies involving large numbers of homogeneous IPF patients are warranted.

Show MeSH
Related in: MedlinePlus