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Silencing CD36 gene expression results in the inhibition of latent-TGF-beta1 activation and suppression of silica-induced lung fibrosis in the rat.

Wang X, Chen Y, Lv L, Chen J - Respir. Res. (2009)

Bottom Line: The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups.The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups.The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China. c_water@hotmail.com

ABSTRACT

Background: The biologically active form of transforming growth factor-beta1 (TGF-beta1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-beta1 (L-TGF-beta1) to active TGF-beta1. To clarify the role of CD36 in the development of silica-induced lung fibrosis, a rat silicosis model was used to observe both the inhibition of L-TGF-beta1 activation and the antifibrotic effect obtained by lentiviral vector silencing of CD36 expression.

Methods: The rat silicosis model was induced by intratracheal injection of 10 mg silica per rat and CD36 expression was silenced by administration of a lentiviral vector (Lv-shCD36). The inhibition of L-TGF-beta1 activation was examined using a CCL-64 mink lung epithelial growth inhibition assay, while determination of hydroxyproline content along with pathological and immunohistochemical examinations were used for observation of the inhibition of silica-induced lung fibrosis.

Results: The lentiviral vector (Lv-shCD36) silenced expression of CD36 in alveolar macrophages (AMs) obtained from bronchoalveolar lavage fluid (BALF) and the activation of L-TGF-beta1 in the BALF was inhibited by Lv-shCD36. The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups. The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups. The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups.

Conclusion: These results indicate that silencing expression of CD36 can result in the inhibition of L-TGF-beta1 activation in a rat silicosis model, thus further preventing the development of silica-induced lung fibrosis.

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Hydroxyproline content of rat lungs. There was no significant difference in the hydroxyproline content of the four groups at 7 days after instillation. The hydroxyproline content of the silica, the silica+Lv-shCD36, and the silica+Lv-shCD36-NC groups was significantly higher than that of the saline control group at 21 and 28 days after instillation. The hydroxyproline content of the silica+Lv-shCD36 group was significantly lower than the silica and silica+Lv-shCD36-NC groups at 21 and 28 days after instillation. Each bar represents the mean ± SEM. *P < 0.05, as compared to the saline control group;ΔP < 0.05, as compared to the silica group; and #P < 0.05, as compared to the silica+Lv-shCD36-NC group. The data represent the means from experiments done in eight rats.
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Figure 3: Hydroxyproline content of rat lungs. There was no significant difference in the hydroxyproline content of the four groups at 7 days after instillation. The hydroxyproline content of the silica, the silica+Lv-shCD36, and the silica+Lv-shCD36-NC groups was significantly higher than that of the saline control group at 21 and 28 days after instillation. The hydroxyproline content of the silica+Lv-shCD36 group was significantly lower than the silica and silica+Lv-shCD36-NC groups at 21 and 28 days after instillation. Each bar represents the mean ± SEM. *P < 0.05, as compared to the saline control group;ΔP < 0.05, as compared to the silica group; and #P < 0.05, as compared to the silica+Lv-shCD36-NC group. The data represent the means from experiments done in eight rats.

Mentions: Hydroxyproline content is an important indicator of lung fibrosis. In this study, no significant differences in the hydroxyproline content of the four treatment groups were observed at 7 days after instillation when measured using a hydroxyproline kit. However, the hydroxyproline contents of the silica group and the silica+Lv-shCD36-NC group were significantly higher than those of the saline control group (P < 0.05) at 21 and 28 days after instillation. The hydroxyproline content of the silica+Lv-shCD36 group was significantly lower than in the silica group and the silica+Lv-shCD36-NC group (P < 0.05), and significantly higher than that of the saline control group (P < 0.05) at 21 and 28 days after instillation (Figure 3).


Silencing CD36 gene expression results in the inhibition of latent-TGF-beta1 activation and suppression of silica-induced lung fibrosis in the rat.

Wang X, Chen Y, Lv L, Chen J - Respir. Res. (2009)

Hydroxyproline content of rat lungs. There was no significant difference in the hydroxyproline content of the four groups at 7 days after instillation. The hydroxyproline content of the silica, the silica+Lv-shCD36, and the silica+Lv-shCD36-NC groups was significantly higher than that of the saline control group at 21 and 28 days after instillation. The hydroxyproline content of the silica+Lv-shCD36 group was significantly lower than the silica and silica+Lv-shCD36-NC groups at 21 and 28 days after instillation. Each bar represents the mean ± SEM. *P < 0.05, as compared to the saline control group;ΔP < 0.05, as compared to the silica group; and #P < 0.05, as compared to the silica+Lv-shCD36-NC group. The data represent the means from experiments done in eight rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2698900&req=5

Figure 3: Hydroxyproline content of rat lungs. There was no significant difference in the hydroxyproline content of the four groups at 7 days after instillation. The hydroxyproline content of the silica, the silica+Lv-shCD36, and the silica+Lv-shCD36-NC groups was significantly higher than that of the saline control group at 21 and 28 days after instillation. The hydroxyproline content of the silica+Lv-shCD36 group was significantly lower than the silica and silica+Lv-shCD36-NC groups at 21 and 28 days after instillation. Each bar represents the mean ± SEM. *P < 0.05, as compared to the saline control group;ΔP < 0.05, as compared to the silica group; and #P < 0.05, as compared to the silica+Lv-shCD36-NC group. The data represent the means from experiments done in eight rats.
Mentions: Hydroxyproline content is an important indicator of lung fibrosis. In this study, no significant differences in the hydroxyproline content of the four treatment groups were observed at 7 days after instillation when measured using a hydroxyproline kit. However, the hydroxyproline contents of the silica group and the silica+Lv-shCD36-NC group were significantly higher than those of the saline control group (P < 0.05) at 21 and 28 days after instillation. The hydroxyproline content of the silica+Lv-shCD36 group was significantly lower than in the silica group and the silica+Lv-shCD36-NC group (P < 0.05), and significantly higher than that of the saline control group (P < 0.05) at 21 and 28 days after instillation (Figure 3).

Bottom Line: The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups.The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups.The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China. c_water@hotmail.com

ABSTRACT

Background: The biologically active form of transforming growth factor-beta1 (TGF-beta1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-beta1 (L-TGF-beta1) to active TGF-beta1. To clarify the role of CD36 in the development of silica-induced lung fibrosis, a rat silicosis model was used to observe both the inhibition of L-TGF-beta1 activation and the antifibrotic effect obtained by lentiviral vector silencing of CD36 expression.

Methods: The rat silicosis model was induced by intratracheal injection of 10 mg silica per rat and CD36 expression was silenced by administration of a lentiviral vector (Lv-shCD36). The inhibition of L-TGF-beta1 activation was examined using a CCL-64 mink lung epithelial growth inhibition assay, while determination of hydroxyproline content along with pathological and immunohistochemical examinations were used for observation of the inhibition of silica-induced lung fibrosis.

Results: The lentiviral vector (Lv-shCD36) silenced expression of CD36 in alveolar macrophages (AMs) obtained from bronchoalveolar lavage fluid (BALF) and the activation of L-TGF-beta1 in the BALF was inhibited by Lv-shCD36. The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups. The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups. The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups.

Conclusion: These results indicate that silencing expression of CD36 can result in the inhibition of L-TGF-beta1 activation in a rat silicosis model, thus further preventing the development of silica-induced lung fibrosis.

Show MeSH
Related in: MedlinePlus