Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats

Mohammad Shoeb,Aaron Erdely,Gul Mustafa,Christina Umbright,James M Antonini,Breanne Y Farris,Pius Joseph,Vamsi Kodali,Jenny R Roberts

doi:10.1038/s41598-017-17645-y

Mohammad Shoeb, Aaron Erdely + Show 7 more

Open Access

https://doi.org/10.1038/s41598-017-17645-y

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Abstract

Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m3 of silica × 6 h/d × 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

Highlights

It is estimated that approximately 1.7 million U.S workers are exposed to respirable crystalline silica in a number of occupations and industries, including mining, construction, and sandblasting[1]
It is our hypothesis that changes in telomere length and the genes involved in telomere regulation may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung diseases, such as fibrosis and tumorigenesis
Inhalation of silica is a known occupational hazard characterized by the progression from pulmonary inflammation and cellular injury to fibrosis, and the possible development of lung cancer[1,4]

Summary

Introduction

It is estimated that approximately 1.7 million U.S workers are exposed to respirable crystalline silica in a number of occupations and industries, including mining, construction, and sandblasting[1]. Silicosis is an irreversible chronic lung disease characterized by inflammation, alveolar proteinosis, and diffuse fibrosis, resulting in progressive restrictive lung function after prolonged exposure to crystalline silica[2]. The measurement of telomere length and/or the expression of proteins that regulate telomeres may serve as potential biomarkers to assess past silica exposure and possibly predict future development of silicosis. The goal of the current study was to assess the effect of silica inhalation exposure on telomere length and the regulation of RTEL1 and TERT gene expression involved in telomere maintenance in the blood and lung tissue in vivo. It is our hypothesis that changes in telomere length and the genes involved in telomere regulation may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung diseases, such as fibrosis and tumorigenesis

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