Effect of high glucose on PKC and MMPs/TIMPs in human mesangial cells.
- Author:
Jinghua YANG
1
;
Qiaoling ZHOU
;
Yanhui WANG
;
Kanghan LIU
;
Jun ZHANG
Author Information
1. Department of Nephrology, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Cells, Cultured;
Glucose;
adverse effects;
pharmacology;
Humans;
Hyperglycemia;
metabolism;
Matrix Metalloproteinase 2;
metabolism;
Matrix Metalloproteinase 9;
metabolism;
Mesangial Cells;
metabolism;
Protein Kinase C;
metabolism;
Protein Kinase Inhibitors;
pharmacology;
RNA, Messenger;
metabolism;
Tissue Inhibitor of Metalloproteinase-1;
metabolism;
Tissue Inhibitor of Metalloproteinase-2;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2009;34(5):425-431
- CountryChina
- Language:Chinese
-
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.
