期刊
JCI INSIGHT
卷 1, 期 18, 页码 -出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.88646
关键词
-
资金
- NHLBI NIH HHS [R01 HL121019, R01 HL133545, R01 HL117062, R01 HL114709, R01 HL132318] Funding Source: Medline
- NIAMS NIH HHS [R01 AR059115] Funding Source: Medline
- NIDDK NIH HHS [R01 DK096030] Funding Source: Medline
- RRD VA [I01 RX001477] Funding Source: Medline
- BLRD VA [I01 BX000976] Funding Source: Medline
- VA [956618, 5I01RX001477-04] Funding Source: Federal RePORTER
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/EBP beta. 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据