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Information Seminar Paper

Title

THE ROLE OF MICRORNA-146A ON NF-ΚB, TRAF6 AND IRAK1 GENE EXPRESSION LEVELS IN HUMAN VASCULAR ENDOTHELIAL CELLS DURING HYPERGLYCEMIC CONDITIONS

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Abstract

 INTRODUCTION: NOWADAYS, IT HAS BEEN BELIEVED THAT DIABETES MELLITUS IS A CHRONIC PROGRESSIVE METABOLIC DISORDER CHARACTERIZED BY HYPERGLYCEMIA, AND ASSOCIATES WITH INCREASED PREVALENCE OF MICRO VASCULAR COMPLICATIONS. EMERGING STUDIES HAVE SHOWN THAT MICRORNA-146A (MIR- 146A) EXPRESSION LEVEL IS ALTERED IN DIABETIC PATIENTS AND ANIMALS. THIS STUDY WAS DESIGNED TO EVALUATE THE ROLE OF MIR-146A ON NF-ΚB, TRAF6 AND IRAK1 GENE EXPRESSION LEVELS IN HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS (HUVECS) DURING HYPERGLYCEMIC CONDITION.METHODS: HUVECS WERE CULTURED IN NORMO- (5 MM) AND HYPERGLYCEMIC (25 MM, 24 H) CONDITIONS. MIR-146A EXPRESSION AND THE MESSENGER RNA EXPRESSION OF NF-ΚB, TRAF6 AND IRAK1 WERE EXAMINED WITH OR WITHOUT MIR-146A MIMIC OR ANTAGOMIR TRANSFECTION USING QUANTITATIVE REAL-TIME PCR.RESULTS: HYPERGLYCEMIA SIGNIFICANTLY UPREGULATED NF-ΚB GENE EXPRESSION (AS AN INFLAMMATION INDEX) IN CULTURED HUVECS. HYPERGLYCEMIA ALSO LEADS TO HIGHER GENE EXPRESSION LEVEL OF MIR-146A, TRAF6 AND IRAK1. WHILE TRANSFECTION OF MIR-146A MIMIC SUBSTANTIALLY SUPPRESSED IRAK-1 EXPRESSION LEVEL, IT INCREASED TRAF-6 AND NF-ΚB MRNAS IN HUVECS DURING HYPERGLYCEMIC CONDITIONS. CONVERSELY, KNOCKDOWN OF MIR-146A BY TRANSFECTION OF MIR-146A ANTAGOMIR INCREASED IRAK-1 AND TRAF-6, AND DECREASED NF-ΚB LEVELS SIGNIFICANTLY.CONCLUSION: THESE DATA SUGGEST THAT MIR146A IS UP REGULATED IN HYPERGLYCEMIC CONDITIONS AS A COMPENSATORY RESPONSE TO REGULATE NF-ΚB ACTIVITY IN HUVECS.

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