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


CONCLUSIONS
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.
Wang
Xin
X
Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China. c_water@hotmail.com
Chen
Ying
Y
Lv
Lina
L
Chen
Jie
J
D000595:Amino Acid Sequence; D000818:Animals; D018955:CD36 Antigens / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D020868:Gene Silencing; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008297:Male; D008907:Mink; D010446:Peptide Fragments / Q000737:chemistry; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000517:prevention & control*; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
D018955:CD36 Antigens; D017931:DNA Primers; D010446:Peptide Fragments; D053773:Transforming Growth Factor beta1; D012313:RNA; D012822:Silicon Dioxide