Background The pathogenesis of silicosis is not clarified. To explore its pathogenesis can provide indicators for the treatment of silicosis fibrosis.
Objective This experiment investigates the role of transforming growth factor-β1 (TGF-β1)/excellular signal-regulated kinase 5 (ERK5) signaling pathway in pulmonary fibrosis.
Methods Healthy male Wistar rats of SPF grade (n=21) were randomly divided into a control group, a model group, and an intervention group, 7 rats per group. The model group and the intervention group were treated with one-time non-exposure method to establish an acute silica exposure model. After 24 h, the rats in the intervention group were intraperitoneally injected with 0.8 mL of Disitertide solution (1 mg Disitertide powder dissolved in 1 mL DMSO and 9 mL normal saline), and the rats in the model group were intraperitoneally injected with 0.8 mL of solvent (1 mL DMSO and 9 mL normal saline), once every 3 d. After the rats were anesthetized, the left upper lobe tissue samples were paraffin-embedded, sliced, and stained with HE and Masson; the right lower lobe tissues were sampled to detect the protein levels of mitogen-activated protein kinase kinase kinase 2 (MEKK2), mitogen-activated protein kinase kinase kinase 3 (MEKK3), phospho-mitogen activated protein kinase kinase 5 (P-MEK5), and phospho-excellular signal-regulated kinase 5 (P-ERK5) by Western blotting; the level of TGF-β1 in serum was detected by ELISA.
Results Compared with the control group, the pathological changes of lungs in the model group and the intervention group were significantly aggravated, and the pathological changes in the intervention group were reduced compared with the model group. The results of Western blotting showed that compared with the control group, the expression levels of MEKK2, MEKK3, P-MEK5, and P-ERK5 in the model group and the intervention group were significantly increased (P < 0.05); but compared with the model group, the expression levels of the four indicators in the intervention group were significantly decreased (P < 0.05). The results of ELISA showed that compared with the control group, the contents of TGF-β1 in the model group and the intervention group were significantly increased (P < 0.05); compared with the model group, the content of TGF-β1 in the intervention group was significantly decreased (P < 0.05).
Conclusion Inhibition of TGF-β1/ERK5 signaling pathway can reduce the expression of TGF-β1 and its downstream signaling proteins MEKK2, MEKK3, P-MEK5, and P-ERK5, thus inhibiting rat silicosis fibrosis.
DownLoad: