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  • Title: [Effect of high glucose on PKC and MMPs/TIMPs in human mesangial cells].
    Author: Yang J, Zhou Q, Wang Y, Liu K, Zhang J.
    Journal: Zhong Nan Da Xue Xue Bao Yi Xue Ban; 2009 May; 34(5):425-31. PubMed ID: 19483291.
    Abstract:
    OBJECTIVE: To explore the relationship between protein kinase C (PKC) and matrix metalloproteinase (MMPs)/tissue inhibitor of metalloproteinase (TIMPs) in human mesangial cells under the high glucose medium, and to analyze the effect of PKC and MMPs/TIMPs in diabetes nephropathy (DN). METHODS: Normal human mesangial cells (NHMC) were divided into 4 groups: a control group(N, 5 mmol/L glucose), a high glucose group (H, 30 mmol/L glucose), a PKC inhibition group (P, 30 mmol/L glucose plus 10-5 mol/L chelerythrine chloride), and an mannitol group (M, 5 mmol/L glucose plus 25 mmol/L mannitol). Cell proliferation was measured by MTT at 24,48 or 72 hours. The activity of PKC was measured by ELISA and the mRNA and protein expressions of MMP2, 9 and TIMP1, 2 were examined by RT-PCR and Western blot. RESULTS: High glucose increased the activity of PKC as well as the expressions of mRNA and protein of MMP2, 9 and TIMP1, 2.The ratio of MMP-2/TIMP-2 and MMP-9/TIMP-1 was significantly decreased in the high glucose group compared with that of the control group (P<0.05). The mRNA and protein expressions of MMP2, 9 and TIMP1 were significantly increased in the PKC inhibition group compared with the control group (P<0.01). The ratio of MMP-2/TIMP-2 and MMP-9/TIMP-1 increased in the inhibition group compared with that of the high glucose group (P<0.05 or P<0.01). The activity of PKC was negatively correlated with the protein ratio of MMP-2/TIMP-2 and MMP-9/TIMP-1(rý-0.651,rý-0.702, both P<0.05). CONCLUSION: High glucose can activate PKC in mesangial cells. The activity of PKC influences the expression of MMPs/TIMPs in the progressing of DN.
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