Suppression of Foxo3-Gatm by miR-132-3p Accelerates Cyst Formation by Up-Regulating ROS in Autosomal Dominant Polycystic Kidney Disease

• Published in: Biomolecules & therapeutics 2021, 29(3), , pp.311-320
• Main Authors: Choi, Seonju, Kim, Do Yeon, Ahn, Yejin, Lee, Eun Ji, Park, Jong Hoon
• Format: Article
• Language: English
• Subjects: Original; 약학
• ISSN: 1976-9148; 2005-4483
• DOI: 10.4062/biomolther.2020.197

Accumulation of reactive oxygen species (ROS) is associated with the development of various diseases. However, the molecular mechanisms underlying oxidative stress that lead to such diseases like autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Here, we observed that oxidative stress markers were increased in :HoxB7-Cre mice. Forkhead transcription factors of the O class (FOXOs) are known key regulators of the oxidative stress response, which have been observed with the expression of FoxO3a in an ADPKD mouse model in the present study. An integrated analysis of two datasets for differentially expressed miRNA, such as miRNA sequencing analysis of conditional knockout mice and microarray analysis of samples from ADPKD patients, showed that miR-132-3p was a key regulator of FOXO3a in ADPKD. miR-132-3p was significantly upregulated in ADPKD which directly targeted in both mouse and human cell lines. Interestingly, the mitochondrial gene was downregulated in ADPKD which led to a decreased inhibition of . Overexpression of miR-132-3p coupled with knockdown of and increased ROS and accelerated cyst formation in 3D culture. This study reveals a novel mechanism involving miR-132-3p, , and that is associated with the oxidative stress that occurs during cystogenesis in ADPKD.