[The inhibitory effect of latent transforming growth factor β1 activation and silicosis by CD36 targeted RNA interference in silicosis model of rat].
OBJECTIVE
To investigate the inhibitory effects of CD36-targeting RNA interference on the latent transforming growth factor β1 (L-TGF-β1) activation and silicotic fibrosis in rat silicosis model.


METHODS
Wistar rats were divided into four groups: saline control group (n=24), SiO2 model group (10 mg SiO2 per rat) (n=24), SiO2+Lv-shCD36 group (lentiviral vector expressing specific shRNA against CD36) (n=24), and SiO2+Lv-shCD36-NC group (non-silence control lentivirus) (n=24). At 7, 21, and 28 d after instillation, the rats were sacrificed. The activity of TGF-β1 in bronchoalveolar lavage fluid (BALF) was measured by evaluating its inhibitory effect on the proliferation of mink lung epithelial cells. The pathological changes of lung tissue were observed by HE staining and van Gieson staining. The hydroxyproline content in the lungs was determined by alkaline lysis method.


RESULTS
At 7 d after instillation, the expression of CD36 mRNA in alveolar macrophages was significantly lower in the SiO2+Lv-shCD36 group than in the saline control group, SiO2 model group, and SiO2+Lv-shCD36-NC group (P < 0.05); the quantity and percentage of active TGF-β1 in BALF were significantly lower in the SiO2+Lv-shCD36 group than in the SiO2 model group and SiO2+Lv-shCD36-NC group (P < 0.05). At 28 d after instillation, there were cellular silicotic nodules in the lungs of rats in SiO2+Lv-shCD36 group and fibrotic cellular silicotic nodules in the lungs of rats in SiO2 model group and SiO2+Lv-shCD36-NC group. At 21 and 28 d after instillation, the hydroxyproline content was significantly lower in the SiO2+Lv-shCD36 group than in the SiO2 model group and SiO2+Lv-sh CD36-NC group (P < 0.05).


CONCLUSIONS
CD36-targeting RNA interference has inhibitory effects on the L-TGF-β1 activation and silicotic fibrosis in rat silicosis model.
Tianjin Centersfor Disease Control and Prevention, Tianjin 300011, China.
Xin
X
Wang
Yan-rang
YR
Wang
De-yi
DY
Yang
Ming
M
Zhang
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006909:Hydroxyproline / Q000737:chemistry; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000378:metabolism / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D018955:CD36 Antigens; D053773:Transforming Growth Factor beta1; D012822:Silicon Dioxide; D006909:Hydroxyproline