Effect of tranilast on cardiac fibroblasts proliferation and phenotype transformation incubated with high concentration of glucose / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect of tranilast on cardiac fibroblasts proliferation and phenotype transformation incubated with a high concentration of glucose and the possible mechanism. METHODS The cardiac fibroblasts were divided into seven groups in accordance with different nutrient solutionsnormal control group(5.5 mmol · L-1 glucose),hypertonic group(5.5 mmol · L-1 glucose+mannitol 25 mmol · L- 1),high glucose group (25 mmol · L- 1 glucose),tranilast intervention groups (25 mmol·L-1 glucose+tranilast 50,100 and 200μmol·L-1),and activin receptor-like kinase 7(ALK7) inhibitor group(25 mmol · L-1 glucose+10μmol · L-1 SB431542). The cell proliferation was detected by MTT method. The transformation of cardiac fibroblasts was determined by immunfluorescence staining. The expression of fibroblast specific protein 1 (FSP-1),α-smooth muscle actin (α-SMA),transforming growth factor-β1(TGF-β1)and ALK7 was assessed by Western blotting. RESULTS Compared with nor?mal control group,A492 nm of cells in high glucose group was significantly increased(P<0.01),while the expression of α-SMA,TGF-β1 and ALK7 protein in high glucose group was significantly increased(P<0.01),but FSP-1 protein was significantly decreased(P<0.01). There was no difference between normal control group and hypertonic group. Compared with high glucose group,A492 nm of cells in tranilast or SB431542 intervention groups were decreased(P<0.05),and the expression of α-SMA,TGF-β1 and ALK7 protein was significantly decreased(P<0.05),but the expression of FSP-1 protein was increased (P<0.05)in tranilast or SB431542 intervention groups. CONCLUSION Tranilast can inhibit the proliferation and phenotype transformation of cardiac fibroblasts induced by high glucose,which may be related to down-regulation of the expression of ALK7.