OBJECTIVE: Low-molecular-weight heparins (LMWH) can inhibit proliferation of glomerular mesangial cells (GMCs) and it is a major and effective drug in the treatment of renal diseases but the mechanism has still not been explained. This paper studies the mechanism by which LMWH inhibits monocyte chemoaltractant protein-1 (MCP-1) expression, secretion and regulation in rat GMCs. METHODS: Three groups were established; GMCs group, LPS group (GMCs+ LPS) and LMWH group (GMCs + LPS + LMWH). GMCs proliferation was detected by MIT at 24 and 48 hs after culture. MCP-1 and nuclear transcriptional factor of Kappa B ( NF-κB) expressions were assayed by immunohistochemistry at 48 h after curture. MCP-1 concentration was determined by EL1SA. RESULTS: In the LMWH group with the terminal concentration of 250 IU/ml, the proliferative rate of GMCs was lower than that in the LPS group and was also lower than those in the LMWH groups with the terminal concentration of 2. 5 IU/ml and 25 IU/ml respectively ( P < 0.05). The proliferative inhibition of GMCs induced by LMWH of three different terminal concentrations was more significant at 48 h than at 24 h after culture. The positive rate of MCP-1 expression of GMCs in the LMWH group with the terminal concentration of 250 IU/ml was obviously lower than that in the LPS group at 48 h afterculture ( P <0.01), but there was no statistical difference when compared with the concentration in the GMCs group. The pasitive rale of MCP-1 expression of GMCs in the LPS group was obviously higher than that in the GMCs group ( P < 0.01). There was no statistical difference in the NF-κB expression at 48 h after culture between the LMWH group and LPS group as well as the GMCs group, while it was obviously higher in the LPS group than that in the GMCs group ( P < 0.01). The MCP-1 concentration in the LMWH group with the terminal concentration of 250 IU/ml was significantly lower than that in the LPS group ( P < 0.01) and did not differ from that in the GMCs group. CONCLUSIONS: LMWH can obviously inhibit proliferation of GMGs, down-regulate the abnormal expression and secretion of MCP-1, but can not inhibit the activity of NF-icB."/>
Mechanism of Inhibiting Rat Glomerular Mesangial Cells Proliferation by LowMolecular Weight Heparins
Abstract OBJECTIVE: Low-molecular-weight heparins (LMWH) can inhibit proliferation of glomerular mesangial cells (GMCs) and it is a major and effective drug in the treatment of renal diseases but the mechanism has still not been explained. This paper studies the mechanism by which LMWH inhibits monocyte chemoaltractant protein-1 (MCP-1) expression, secretion and regulation in rat GMCs. METHODS: Three groups were established; GMCs group, LPS group (GMCs+ LPS) and LMWH group (GMCs + LPS + LMWH). GMCs proliferation was detected by MIT at 24 and 48 hs after culture. MCP-1 and nuclear transcriptional factor of Kappa B ( NF-κB) expressions were assayed by immunohistochemistry at 48 h after curture. MCP-1 concentration was determined by EL1SA. RESULTS: In the LMWH group with the terminal concentration of 250 IU/ml, the proliferative rate of GMCs was lower than that in the LPS group and was also lower than those in the LMWH groups with the terminal concentration of 2. 5 IU/ml and 25 IU/ml respectively ( P < 0.05). The proliferative inhibition of GMCs induced by LMWH of three different terminal concentrations was more significant at 48 h than at 24 h after culture. The positive rate of MCP-1 expression of GMCs in the LMWH group with the terminal concentration of 250 IU/ml was obviously lower than that in the LPS group at 48 h afterculture ( P <0.01), but there was no statistical difference when compared with the concentration in the GMCs group. The pasitive rale of MCP-1 expression of GMCs in the LPS group was obviously higher than that in the GMCs group ( P < 0.01). There was no statistical difference in the NF-κB expression at 48 h after culture between the LMWH group and LPS group as well as the GMCs group, while it was obviously higher in the LPS group than that in the GMCs group ( P < 0.01). The MCP-1 concentration in the LMWH group with the terminal concentration of 250 IU/ml was significantly lower than that in the LPS group ( P < 0.01) and did not differ from that in the GMCs group. CONCLUSIONS: LMWH can obviously inhibit proliferation of GMGs, down-regulate the abnormal expression and secretion of MCP-1, but can not inhibit the activity of NF-icB.
