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Selective tubular activation of hypoxia-inducible factor-2α has dual effects on renal fibrosis

Authors
 Kyoung Hye Kong  ;  Hyung Jung Oh  ;  Beom Jin Lim  ;  Minsuk Kim  ;  Ki-Hwan Han  ;  Youn-Hee Choi  ;  Kihwan Kwon  ;  Bo Young Nam  ;  Kyoung Sook Park  ;  Jung Tak Park  ;  Seung Hyeok Han  ;  Tae-Hyun Yoo  ;  Shina Lee  ;  Seung-Jung Kim  ;  Duk-Hee Kang  ;  Kyu Bok Choi  ;  Vera Eremina  ;  Susan E. Quaggin  ;  Dong-Ryeol Ryu  ;  Shin-Wook Kang 
Citation
 Scientific Reports, Vol.7(1) : 11351, 2017 
Journal Title
 Scientific Reports 
Issue Date
2017
Abstract
Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase. In CKD mice, activation of HIF-2α at the beginning of CKD significantly aggravated renal fibrosis, whereas it did not lead to renal dysfunction. However, activation at a late-stage of CKD abrogated both renal dysfunction and fibrosis, which was associated with restoration of renal vasculature and amelioration of hypoxia through increased renal tubular expression of VEGF and its isoforms. As with tubular cells with HIF-2α activation, those under hypoxia also upregulated VEGF, fibronectin, and type 1 collagen expressions associated with HIF-1α activation. In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD.
Files in This Item:
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DOI
10.1038/s41598-017-11829-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
강신욱(Kang, Shin Wook) ORCID logo https://orcid.org/0000-0002-5677-4756
박정탁(Park, Jung Tak) ORCID logo https://orcid.org/0000-0002-2325-8982
유태현(Yoo, Tae Hyun) ORCID logo https://orcid.org/0000-0002-9183-4507
임범진(Lim, Beom Jin) ORCID logo https://orcid.org/0000-0003-2856-0133
한승혁(Han, Seung Hyeok) ORCID logo https://orcid.org/0000-0001-7923-5635
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160813
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