Interaction between matrix metalloproteinases and interleukin-4 in type 2 diabetes mellitus

• Main Authors: Yi-Ching, 黃怡晴
• Other Authors: 張懿欣
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/32744679000254872218

碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 94 === Diabetes mellitus (DM) is a common endocrine disease with unknown etiology. Immune response and inflammation are suggested to play important roles in the development and complications of type 2 diabetes mellitus (T2DM). Our previous studies revealed that individuals carrying genotypes of high interleukin-4 (IL-4) secreting ability and higher IL-4 levels were susceptible to diabetic development. Several studies documented that MMP2 and MMP9 were down-regulated in diabetic nephropathy. However, whether and to what degree hyperglycemia affects the expression and activity of the MMPs induction/activation system in patients with diabetes remains unknown. Therefore, we designed to examine the putative cross talk between inflammation and MMP system by investigating the putative regulation and effect of IL-4 to MMP expression by using 3T3-L1 cells to further elucidate the roles of MMP and IL-4 in the pathogenesis of T2DM. Our data showed that MMP2 mRNA expression was increased in 3T3-L1 fibroblasts by pre-treatment of IL-4 for 30 min and then chronic insulin for 18 hrs under high glucose condition in contrast of control without any treatment. The MMP9 mRNA expression was increased by treatment of IL-4 and/or insulin under high glucose condition in contrast of control without any treatment. We detect MMP2 and MMP9 activity by using gelatin-zymography analysis. We find that the MMP2 activity was decreased by treatment of IL-4 for 30 min or acute insulin for 30 min or pre-treatment of IL-4 for 30 min and then acute insulin for 30 min under high glucose condition in contrast of control without any treatment. But, the MMP2 activity was increased by treatment of chronic insulin for 18 hrs or pre-treatment of IL-4 for 30 min and then treatment of chronic insulin for 18 hrs under high glucose condition in contrast of control without any treatment. Otherwise, the MMP9 activity was decreased by treatment of IL-4 for 30 min or pre-treatment of IL-4 for 30 min and then acute insulin for 30 min under high glucose condition in contrast of control without any treatment. The MMP9 activity was increased fibroblasts by treatment of chronic insulin for 18 hrs or acute insulin for 30 min or pre-treatment of IL-4 for 30 min and then chronic insulin for 18 hrs under high glucose condition in contrast of control without any treatment. Besides, we find that MMP2 activity was increased fibroblasts by pre-treatment of IL-4 for 30 min under low glucose condition and then insulin in high or low glucose condition in contrast of control with only pre-treatment of IL-4 for 30 min under low glucose condition. The MMP9 activity was decreased by pre-treatment of IL-4 for 30 min under low glucose condition and then chronic insulin for 18 hrs in contrast of control with only pre-treatment of IL-4 for 30 min. But, the MMP9 activity was increased by pre-treatment of IL-4 for 30 min and then acute insulin for 30 min under high or low glucose condition in contrast of control with only pre-treatment of IL-4 for 30 min in low glucose condition. Using well-differentiation technique, 3T3-L1 fibroblasts were induced to 3T3-L1 adipocytes. We find that the MMP2 mRNA expression was decreased and the MMP9 mRNA expression was increased in 3T3-L1 adipocytes by treatment of IL-4 for 30 min or acute insulin for 30 min or chronic insulin for 18 hrs or pre-treatment of IL-4 for 30 min and then insulin under high glucose condition in contrast f control without any treatment. This common form of diabetes is often associated with obesity. Adipose tissues will secrete many adipocytokines and play a role in energy balance. Thus, we can evidence the putative mechanism of IL-4 regulation to MMPs system in type 2 diabetes. Above all, we can suggest that IL-4 may be involved in some complications of diabetes by regulating MMPs system.