Gene Expression of Surfactant Protein‐A and Thyroid Transcription Factor‐1 in Lungs of Rats Exposed to Silicon‐Carbide Whisker in vivo

Abstract

No clear tendency to the expression of SP-C was observed, but the patterns of expression of TTF-1 and SP-A were similar. These data suggest that SP-A and TTF-1 are associated with not only the acute phase but also the chronic phase in lungs exposed to SiCW. As occupational and environmental inhalation exposure to asbestos causes pulmonary fibrosis 1) , a number of manmade mineral fibers (MMMFs) have been developed as a substitute, but, because of their similar physiochemical properties, MMMFs are thought to have adverse biological effects similar to those of asbestos 2) . Animal studies have shown that silicon carbide whisker (SiCW), which is used in abrasive and refractory materials, and the production of parts for electronic equipment, cause fibrosis 3,4) , suggesting that SiCW might have a fibrogenic potential.Surfactant protein 5) produced by mainly type II alveolar epithelial cells acts as a control tower responsible for guiding the secretion and re-uptake of phospholipid which decreases alveolar surface tension, and through the prevention of alveolar collapse, these are thought to play contributory roles in preventing the progress of fibrotic processes 6,7) . Decreases in the levels of SP-A and SP-C mRNA have been reported to occur in the bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis 5,8) , and SP-A is thought to be a good biomarker of lung injury and pulmonary fibrotic activity.Furthermore, thyroid transcription factor-1 (TTF-1) 9) , a common transcription factor of SP-A and SP-C mRNA, is involved in tissue-specific gene expression of epithelial (SiCW), an asbestos substitute, produces pulmonary fibrotic changes, suggesting that SICW might have a fibrogenic potential. It is thought that surfactant protein is a good biomarker of lung injury and pulmonary fibrotic activity. In order to explore whether or not surfactant protein is associated with lung disorder through exposure to SiCW, we examined the expression of SP-A, SP-C and thyroid transcription factor-1 (TTF-1), a common transcription factor of SP-A and SP-C mRNA in lungs exposed to SiCW. Male Wistar rats were administered 2 mg or 10 mg of SiCW suspended in saline by a single intratracheal instillation, and were sacrificed at 3 d, 1 wk, 1 month, 3 months and 6 months after the intratracheal instillation. RNA was subsequently extracted from the lungs, and expression of SP-A, SP-C and TTF-1 mRNA from the lungs was observed by reverse transcriptionpolymerase chain reaction (RT-PCR). Exposure to 2 mg of SiCW showed a decrease in mRNA of SP-A and TTF-1 at 6 months, but exposure to 10 mg of SiCW showed decreased levels of SP-A and TTF-1 mRNA at 3 d and 6 months. On the other hand, 2 mg of SiCW increased the level of SP-C mRNA from 3 d to 3 months, and 10 mg of SiCW decreased the levels of SP-C mRNA in the rat lungs at 3 d, 1 month and 6 months.

Thyroid transcription factor-1 (TTF-1/Nkx2.1/TITF1) gene regulation in the lung

“…There is limited information on the regulation of TTF-1 expression in the lung. Intratracheal instillation of silicon carbide whiskers, an asbestos substitute, into rats produced fibrotic changes and decreased the expression of SP-A and TTF-1 [83]. Changes in SP-A and TTF-1 levels were apparent as early as 3 days after the exposure and reduced expression was maintained for up to 6 months following the single exposure.…”

Comparison of acid-induced inflammatory responses in the rat lung during high frequency oscillatory and conventional mechanical ventilation

“…Similarly, cell stretching is important for surfactant production in the injured lung [21]. Surfactant protein is mainly produced by type II alveolar 13 epithelial cells and can be classified into SP-A, -B, -C, and -D types [22]. SP-A is thought to be a good biomarker of lung injury [23].…”