Melatonin Treatment Improves Renal Fibrosis via miR-4516/SIAH3/PINK1 Axis

Cells

Ji Ho Lim¹  Gyeongyun Go¹  Gaeun Lee¹  Jun Hee Lee²  Sang Hun Lee³  Yeo Min Yoon³  Sungtae Yoon⁴ 

[1] Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 31151, Korea;Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea;Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul 04401, Korea;Stembio. Ltd., Entrepreneur 306, Soonchunhyang-ro 22, Sinchang-myeon, Asan 31538, Korea;

关键词: chronic kidney disease;    melatonin;    miR-4516;    mitophagy;    PINK1;    renal fibrosis;   

DOI  :  10.3390/cells10071682

来源: DOAJ

【 摘 要 】

Dysregulation in mitophagy, in addition to contributing to imbalance in the mitochondrial dynamic, has been implicated in the development of renal fibrosis and progression of chronic kidney disease (CKD). However, the current understanding of the precise mechanisms behind the pathogenic loss of mitophagy remains unclear for developing cures for CKD. We found that miR-4516 is downregulated and its target SIAH3, an E3 ubiquitin protein ligase that reduces PINK1 accumulation to damaged mitochondria, is upregulated in the renal cortex of CKD mice. Here, we demonstrated that melatonin injection induces miR-4516 expression and suppresses SIAH3, and promotes PINK1/Parkin-mediated mitophagy. Furthermore, we demonstrated that melatonin injection attenuates the pathological features of CKD by improving mitochondrial homeostasis. Our data supports that mitochondrial autophagy regulation by activating miR-4516/SIAH3/PINK1 mitophagy signaling axis can be a viable new strategy for treating CKD.

【 授权许可】

Unknown