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Fragmentation of kidney epithelial cell primary cilia occurs by cisplatin and these cilia fragments are excreted into the urine

Title
Fragmentation of kidney epithelial cell primary cilia occurs by cisplatin and these cilia fragments are excreted into the urine
Authors
Kong, Min JungBak, Sang HongHan, Ki-HwanKim, Jee InPark, Jeen-WooPark, Kwon Moo
Ewha Authors
한기환
SCOPUS Author ID
한기환scopus
Issue Date
2019
Journal Title
REDOX BIOLOGY
ISSN
2213-2317JCR Link
Citation
REDOX BIOLOGY vol. 20, pp. 38 - 45
Keywords
Primary ciliaROSDeciliationAcute kidney injuryCisplatinAcetylated a-tubulinIDH2
Publisher
ELSEVIER SCIENCE BV
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
The primary cilium, which protrudes from the cell surface, is associated with the pathogenesis of various diseases, including acute kidney injury (AKI). Primary cilium length dynamically changes during the progression of diseases. However, its relevance in disease and the underlying mechanism are largely unknown. In this study, we investigated the role of primary cilia in AM induced by cisplatin, an effective anticancer drug, and the underlying mechanisms. In addition, we evaluated the usefulness of length alteration and deciliation of primary cilia into the urine for the diagnosis of AM. Cisplatin induced shortening, elongation, and normalization of the primary cilia in kidney epithelial cells over time. During shortening, primary cilia fragments and ciliary proteins were excreted into the urine. During deciliation, cell proliferation and the expression of cyclin-dependent kinase inhibitor and proliferating cell nuclear antigen were not significantly changed. Shortening and deciliation of primary cilia were observed before significant increases in plasma creatinine and blood urea nitrogen concentration occurred. Pretreatment with Mito-Tempo, a mitochondria-targeted antioxidant, prevented cisplatin-induced primary cilium shortening and inhibited the increases in superoxide formation, lipid peroxidation, blood urea nitrogen, and tissue damage. In contrast, isocitrate dehydrogenase 2 (Idh2) gene deletion, which results in defect of the NADPH-associated mitochondrial antioxidant system, exacerbated cisplatin-induced changes in mice. Taken together, our findings demonstrate that cisplatin induces deciliation into the urine and antioxidant treatment prevents this deciliation, renal dysfunction, and tissue damage after cisplatin injection. These results suggest that cisplatin-induced AKI is associated with primary cilia and urine primary cilia proteins might be a non-invasive biomarker of kidney injury.
DOI
10.1016/j.redox.2018.09.017
Appears in Collections:
의과대학 > 의학과 > Journal papers
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