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

Autor: Yeo Min Yoon, Gyeongyun Go, Sungtae Yoon, Ji Ho Lim, Gaeun Lee, Jun Hee Lee, Sang Hun Lee
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cells, Vol 10, Iss 7, p 1682 (2021)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells10071682
Popis: 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.
Databáze: Directory of Open Access Journals
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