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

Title
Selective tubular activation of hypoxia-inducible factor-2α has dual effects on renal fibrosis
Authors
Kong K.H.Oh H.J.Lim B.J.Kim M.Han K.-H.Choi Y.-H.Kwon K.Nam B.Y.Park K.S.Park J.T.Han S.H.Yoo T.-H.Lee S.Kim S.-J.Kang D.-H.Choi K.B.Eremina V.Quaggin S.E.Ryu D.-R.Kang S.-W.
Ewha Authors
강덕희최규복권기환한기환류동열최윤희김민석
SCOPUS Author ID
강덕희scopus; 최규복scopus; 권기환scopus; 한기환scopus; 류동열scopus; 최윤희scopus; 김민석scopus
Issue Date
2017
Journal Title
Scientific Reports
ISSN
2045-2322JCR Link
Citation
vol. 7, no. 1
Publisher
Nature Publishing Group
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2017 The Author(s).
DOI
10.1038/s41598-017-11829-2
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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