TY - JOUR T1 - [Effect of bone morphogenetic protein-7 on monocyte chemoattractant protein-1 induced epithelial-myofibroblast transition and TGF-beta1-Smad 3 signaling pathway of HKC cells]. AU - Tan,Xiao-yue, AU - Zheng,Fa-lei, AU - Zhou,Qiu-gen, AU - Duan,Lin, AU - Li,Yan, PY - 2005/12/3/pubmed PY - 2013/6/26/medline PY - 2005/12/3/entrez SP - 2607 EP - 12 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 85 IS - 37 N2 - OBJECTIVE: To examine the effect of Bone Morphogenetic protein-7 (BMP-7) on Monocyte chemoattractant protein-1 (MCP-1) induced epithelial-myofibroblast transition (EMT) in cultured renal proximal tubular cells (HK-2) and the relationship between TGF-beta1-smad 3 expressions and MCP-1 induced EMT. METHODS: The cultured HK-2 cells were divided into six groups: a, negative control, b, treated with TGF-beta1 (5 ng/ml) as positive control, c, treated with MCP-1 (0.1, 1, 10, 50 ng/ml), d, treated with BMP-7 (0.1, 1, 10, 50 ng/ml), e. co-treated with MCP-1 (1 ng/ml) and MCP-1 neutralized antibody (1 ng/ml), f. co-treated with MCP-1 (1 ng/ml) and BMP-7 (50 ng/ml). alpha-Smooth Muscle Actin (alpha-SMA) mRNA expression of HK-2 cells was assessed with RT-PCR. Secretion of type I collagen was assessed with RT-PCR and ELISA, respectively. TGF-beta1 and Smad 3 expressions were assessed with Western blot. RESULTS: alpha-SMA mRNA expression significantly increased in HK-2 cells treated with MCP-1 (0.1, 1 ng/ml) compared with negative controls (5.97 +/- 0.35, 23.36 +/- 1.37 vs. 0.59 +/- 0.38, P < 0.01). alpha-SMA mRNA expression of HK-2 cells concomitantly treated with MCP-1 neutralized antibody or BMP-7 (50 ng/ml) and MCP-1 (1 ng/ml) significantly decreased than that in cells treated with MCP-1 (1 ng/ml) alone (1.93 +/- 0.34, 13.59 +/- 0.38 vs. 36.36 +/- 1.37, P < 0.01). Secretion of type I collagen of the cells treated with MCP-1 (0.1, 1 ng/ml) markedly increased compared with negative control (1751 +/- 34, 1876 +/- 45 vs. 1450 +/- 62; P < 0.01). The secretion of type I collagen of the supernatant were also significantly lower than that in cells treated with MCP-1 (1 ng/ml) alone (1462 +/- 56, 1596 +/- 34 vs. 1876 +/- 45, P < 0.05). The expression of TGF-beta1 and Smad 3 of HK-2 cells treated with MCP-1 (1 ng/ml) were markedly higher than that of negative controls, respectively (36.31 +/- 1.37 vs. 0.75 +/- 0.16, P < 0.01; 56.98 +/- 2.61 vs. 23.05 +/- 1.82, P < 0.01). The expressions of TGF-beta1 and Smad 3 in HK-2 cells treated concomitantly with MCP-1 neutralized antibody or BMP-7 (50 ng/ml) and MCP-1 (1 ng/ml) were markedly decreased than that treated with MCP-1 alone, respectively. (4.61 +/- 0.74, 23.74 +/- 2.14 vs. 36.31 +/- 1.37, P < 0.01; 19.63 +/- 1.65, 37.06 +/- 1.82 vs. 56.98 +/- 2.61, P < 0.01). The expressions of TGF-beta1 and Smad 3 in HK-2 cells treated concomitantly with MCP-1 neutralized antibody or BMP-7 (50 ng/ml) and MCP-1 (1 ng/ml) were markedly decreased than that treated with MCP-1 alone, respectively. (4.61 +/- 0.74, 23.74 +/- 2.14 vs. 36.31 +/- 1.37, P < 0.01; 19.63 +/- 1.65, 37.06 +/- 1.82 vs. 56.98 +/- 2.61, P < 0.01). CONCLUSIONS: The results documented that MCP-1 may induce EMT of HK-2 cells in vitro, and this effect is related to up-regulated expression of TGF-beta1 and Smad 3. BMP-7 may partially inhibit MCP-1-induced EMT and this effect is related to the downregulated expression of TGF-beta1 and Smad 3 of the cells. The results also suggest that MCP-1 induced EMT may involve the TGF-beta1-independent pathway of the cells. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/16321320/[Effect_of_bone_morphogenetic_protein_7_on_monocyte_chemoattractant_protein_1_induced_epithelial_myofibroblast_transition_and_TGF_beta1_Smad_3_signaling_pathway_of_HKC_cells]_ DB - PRIME DP - Unbound Medicine ER -