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LncRNA H19 sponges miR-103-3p to promote the high phosphorus-induced osteoblast phenotypic transition of vascular smooth muscle cells by upregulating Runx2.

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机构: [1]Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, PR China
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关键词: LncRNA H19 miR-103-3p Runx2 Osteoblast phenotypic transition Competing endogenous RNAs

摘要:
Elucidating the mechanism of the osteogenic phenotypic transdifferentiation of vascular smooth muscle cells (VSMCs) is the key to determining the diagnosis and treatment of arterial medial calcification (AMC). Long noncoding RNAs (lncRNAs) have been reported to participate in the regulation of vascular physiology and pathology. Here, we investigated the effect and mechanism of the lncRNA H19 on the osteoblastic differentiation of VSMCs induced by high phosphorus. H19 was expressed at high levels in high phosphorus-induced primary rat VSMCs. Further experiments indicated that H19 played a positive role in the osteoblast phenotypic transition by suppressing miR-103-3p expression and subsequently promoting osteoblast-specific marker expression, including bone morphogenetic protein 2 (BMP-2) and osteopontin (OPN). Mechanistically, we recognized RUNX family transcription factor 2 (Runx2) as a direct target of miR-103-3p. Moreover, H19 directly interacted with miR-103-3p, and overexpression of miR-103-3p reversed the upregulation of Runx2 induced by H19. Therefore, H19 positively regulated Runx2 expression by sponging miR-103-3p and promoted the osteoblast phenotypic transition in VSMC calcification. Collectively, the lncRNA H19 promoted osteogenic differentiation by modulating the miR-103-3p/Runx2 axis in the process of VSMC calcification induced by a high phosphorus concentration. The current study provided new insights into an important role for the lncRNA H19 as a miRNA sponge in VSMCs and supplied novel insights into lncRNA-directed diagnostics and therapeutics for vascular calcification.Copyright © 2021 Elsevier Inc. All rights reserved.

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 3 区 细胞生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 3 区 细胞生物学
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出版当年[2022]版:
Q2 CELL BIOLOGY
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Q2 CELL BIOLOGY

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第一作者机构: [1]Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, PR China
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通讯机构: [1]Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, PR China [*1]Department of Nephrology, the Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang 050011, PR China
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