Abstract

BackgroundIdiopathic 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.MethodsThe 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.ResultsThe 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.ConclusionsThe 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.

Highlights

  • Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown causes

  • We evaluated the expression of mTOR, Zinc finger E-box-binding homeobox 1 (ZEB1), and ROCK1 proteins in the lung tissue, along with clinical parameters such as radiological honeycombing score, histological fibrosis score, pulmonary function, and patient survival rate

  • We first demonstrated that mTOR, ZEB1 and ROCK1 was expressed in hyperplastic alveolar epithelial cells of human pulmonary fibrosis lungs

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Summary

Introduction

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. 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. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, lethal lung disease of unknown cause, histologically defined as usual interstitial pneumonia (UIP) [1]. The initiating injury and subsequent pathways for IPF have not been elucidated, but the disease is considered to be an epithelial fibrotic disorder It is characterized by epithelial injury followed by aberrant wound healing with excessive fibrosis and minimal inflammation. A previously published case study reported that rapamycin was successfully used to treat a patient with IPF [4]

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