Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{a3e9a5fbf0fa4ee5baeacceafe9de4aa,
title = "Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing",
abstract = "The development of vascular calcification (VC) in chronic uremia (CU) is a tightly regulated process controlled by factors promoting and inhibiting mineralization. Next-generation high-throughput RNA sequencing (RNA-seq) is a powerful and sensitive tool for quantitative gene expression profiling and the detection of differentially expressed genes. In the present study, we, for the first time, used RNA-seq to examine rat aorta transcriptomes from CU rats compared with control rats. Severe VC was induced in CU rats, which lead to extensive changes in the transcriptional profile. Among the 10,153 genes with an expression level of >1 reads/kilobase transcript/million mapped reads, 2,663 genes were differentially expressed with 47{\%} upregulated genes and 53{\%} downregulated genes in uremic rats. Significantly deregulated genes were enriched for ontologies related to the extracellular matrix, response to wounding, organic substance, and ossification. The individually affected genes were of relevance to osteogenic transformation, tissue calcification, and Wnt modulation. Downregulation of the Klotho gene in uremia is believed to be involved in the development of VC, but it is debated whether the effect is caused by circulating Klotho only or if Klotho is produced locally in the vasculature. We found that Klotho was neither expressed in the normal aorta nor calcified aorta by RNA-seq. In conclusion, we demonstrated extensive changes in the transcriptional profile of the uremic calcified aorta, which were consistent with a shift in phenotype from vascular tissue toward an osteochondrocytic transcriptome profile. Moreover, neither the normal vasculature nor calcified vasculature in CU expresses Klotho.",
keywords = "Animals, Aorta, Abdominal, Chronic Disease, Gene Expression Profiling, Gene Ontology, Glucuronidase, Male, Rats, Sequence Analysis, RNA, Uremia, Vascular Calcification, Journal Article, Research Support, Non-U.S. Gov't",
author = "Rukov, {Jakob L} and Eva Gravesen and Mace, {Maria L} and Jacob Hofman-Bang and Jeppe Vinther and Andersen, {Claus B} and Ewa Lewin and Klaus Olgaard",
note = "Copyright {\circledC} 2016 the American Physiological Society.",
year = "2016",
month = "3",
day = "15",
doi = "10.1152/ajprenal.00472.2015",
language = "English",
volume = "310",
pages = "F477--91",
journal = "American Journal of Physiology - Renal Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "6",

}

RIS

TY - JOUR

T1 - Effect of chronic uremia on the transcriptional profile of the calcified aorta analyzed by RNA sequencing

AU - Rukov, Jakob L

AU - Gravesen, Eva

AU - Mace, Maria L

AU - Hofman-Bang, Jacob

AU - Vinther, Jeppe

AU - Andersen, Claus B

AU - Lewin, Ewa

AU - Olgaard, Klaus

N1 - Copyright © 2016 the American Physiological Society.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - The development of vascular calcification (VC) in chronic uremia (CU) is a tightly regulated process controlled by factors promoting and inhibiting mineralization. Next-generation high-throughput RNA sequencing (RNA-seq) is a powerful and sensitive tool for quantitative gene expression profiling and the detection of differentially expressed genes. In the present study, we, for the first time, used RNA-seq to examine rat aorta transcriptomes from CU rats compared with control rats. Severe VC was induced in CU rats, which lead to extensive changes in the transcriptional profile. Among the 10,153 genes with an expression level of >1 reads/kilobase transcript/million mapped reads, 2,663 genes were differentially expressed with 47% upregulated genes and 53% downregulated genes in uremic rats. Significantly deregulated genes were enriched for ontologies related to the extracellular matrix, response to wounding, organic substance, and ossification. The individually affected genes were of relevance to osteogenic transformation, tissue calcification, and Wnt modulation. Downregulation of the Klotho gene in uremia is believed to be involved in the development of VC, but it is debated whether the effect is caused by circulating Klotho only or if Klotho is produced locally in the vasculature. We found that Klotho was neither expressed in the normal aorta nor calcified aorta by RNA-seq. In conclusion, we demonstrated extensive changes in the transcriptional profile of the uremic calcified aorta, which were consistent with a shift in phenotype from vascular tissue toward an osteochondrocytic transcriptome profile. Moreover, neither the normal vasculature nor calcified vasculature in CU expresses Klotho.

AB - The development of vascular calcification (VC) in chronic uremia (CU) is a tightly regulated process controlled by factors promoting and inhibiting mineralization. Next-generation high-throughput RNA sequencing (RNA-seq) is a powerful and sensitive tool for quantitative gene expression profiling and the detection of differentially expressed genes. In the present study, we, for the first time, used RNA-seq to examine rat aorta transcriptomes from CU rats compared with control rats. Severe VC was induced in CU rats, which lead to extensive changes in the transcriptional profile. Among the 10,153 genes with an expression level of >1 reads/kilobase transcript/million mapped reads, 2,663 genes were differentially expressed with 47% upregulated genes and 53% downregulated genes in uremic rats. Significantly deregulated genes were enriched for ontologies related to the extracellular matrix, response to wounding, organic substance, and ossification. The individually affected genes were of relevance to osteogenic transformation, tissue calcification, and Wnt modulation. Downregulation of the Klotho gene in uremia is believed to be involved in the development of VC, but it is debated whether the effect is caused by circulating Klotho only or if Klotho is produced locally in the vasculature. We found that Klotho was neither expressed in the normal aorta nor calcified aorta by RNA-seq. In conclusion, we demonstrated extensive changes in the transcriptional profile of the uremic calcified aorta, which were consistent with a shift in phenotype from vascular tissue toward an osteochondrocytic transcriptome profile. Moreover, neither the normal vasculature nor calcified vasculature in CU expresses Klotho.

KW - Animals

KW - Aorta, Abdominal

KW - Chronic Disease

KW - Gene Expression Profiling

KW - Gene Ontology

KW - Glucuronidase

KW - Male

KW - Rats

KW - Sequence Analysis, RNA

KW - Uremia

KW - Vascular Calcification

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1152/ajprenal.00472.2015

DO - 10.1152/ajprenal.00472.2015

M3 - Journal article

VL - 310

SP - F477-91

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1931-857X

IS - 6

ER -

ID: 49588619