ID | 114293 |
Author |
Masuda, Masashi
University of Colorado Denver
Tokushima University Educator and Researcher Directory
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Miyazaki-Anzai, Shinobu
University of Colorado Denver
Keenan, Audrey L.
University of Colorado Denver
Shiozaki, Yuji
University of Colorado Denver
Okamura, Kayo
University of Colorado Denver
Chick, Wallace S.
University of Colorado Denver
Williams, Kristina
University of Colorado Denver
Zhao, Xiaoyun
University of Colorado Denver
Rahman, Shaikh Mizanoor
Texas Tech University
Tintut, Yin
University of California
Adams, Christopher M.
University of Iowa
Miyazaki, Makoto
University of Colorado Denver
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Content Type |
Journal Article
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Description | Emerging evidence indicates that upregulation of the ER stress–induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney disease (CKD). In this study, we demonstrated the pathophysiological role of ATF4 in vascular calcification using global Atf4 KO, smooth muscle cell–specific (SMC-specific) Atf4 KO, and transgenic (TG) mouse models. Reduced expression of ATF4 in global ATF4-haplodeficient and SMC-specific Atf4 KO mice reduced medial and atherosclerotic calcification under normal kidney and CKD conditions. In contrast, increased expression of ATF4 in SMC-specific Atf4 TG mice caused severe medial and atherosclerotic calcification. We further demonstrated that ATF4 transcriptionally upregulates the expression of type III sodium-dependent phosphate cotransporters (PiT1 and PiT2) by interacting with C/EBPβ. These results demonstrate that the ER stress effector ATF4 plays a critical role in the pathogenesis of vascular calcification through increased phosphate uptake in vascular SMCs.
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Journal Title |
JCI Insight
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ISSN | 23793708
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Publisher | American Society for Clinical Investigation
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Volume | 1
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Issue | 18
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Start Page | e88646
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Published Date | 2016-11-03
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Rights | Open Access Journal
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Publisher
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departments |
Medical Sciences
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