Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Dr. Subrata Chakrabarti

Abstract

We examined the role of MALAT1, a highly conserved nuclear lncRNA, in chronic diabetic complications affecting the heart and kidneys, specifically with respect to inflammatory cytokine production. Endothelial cells, exposed to various glucose levels, and MALAT1 knockout mice and controls, with or without streptozotocin-induced diabetes were examined. Endothelial cells cultured with high glucose, and renal and cardiac tissue from diabetic mice showed increased inflammatory cytokine (eg. IL-6, IL1β, TNFα) production along with transient MALAT1 upregulation. This was confirmed by both transcript and protein analyses, and such changes were prevented in the MALAT1 knockout diabetic animals. In the malat1 knockout animals, diabetes-induced cardiac dysfunction was also prevented. We further identified that such actions of MALAT1 are mediated by specific downstream molecules including SAA3 and p53. The data from this study provided direct evidence to the importance of MALAT1 in the pathogenesis of chronic diabetic complications involving the heart and kidneys.


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