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[This article belongs to Volume - 69, Issue - 11]
Published on : 2024-11-06 13:17:29
Article Code: AMJ-06-11-2024-12304
Title : Long Non-Coding RNA MALAT1 Inhibition via Antisense Oligonucleotides Attenuates Diabetic Kidney Disease Progression Through Regulation of Endothelial-Mesenchymal Transition
Author(s) : Dr. Priya Sharma, Dr. Omar Hassan
Abstract :
Endothelial-mesenchymal transition (EndMT) contributes to renal fibrosis in diabetic kidney disease (DKD). We
identified the long non-coding RNA MALAT1 as a key regulator of EndMT in high glucose-stimulated human
glomerular endothelial cells. MALAT1 sponged miR-145, thereby derepressing ZEB2 and promoting endothelial
dysfunction. Systemic administration of gapmer antisense oligonucleotides (ASOs) targeting MALAT1 in db/db
diabetic mice reduced albuminuria by 50%, preserved glomerular endothelial marker expression, and attenuated
interstitial fibrosis. RNA-immunoprecipitation confirmed direct MALAT1-miR-145-ZEB2 axis regulation. LncRNA
targeted therapies represent a novel approach to halt DKD progression.