Weigand, Julia E. ; Boeckel, Jes-Niels ; Gellert, Pascal ; Dimmeler, Stefanie (2012)
Hypoxia-induced alternative splicing in endothelial cells.
In: PloS one, 7 (8)
doi: 10.1371/journal.pone.0042697
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
BACKGROUND
Adaptation to low oxygen by changing gene expression is vitally important for cell survival and tissue development. The sprouting of new blood vessels, initiated from endothelial cells, restores the oxygen supply of ischemic tissues. In contrast to the transcriptional response induced by hypoxia, which is mainly mediated by members of the HIF family, there are only few studies investigating alternative splicing events. Therefore, we performed an exon array for the genome-wide analysis of hypoxia-related changes of alternative splicing in endothelial cells.
METHODOLOGY/PRINCIPAL FINDINGS
Human umbilical vein endothelial cells (HUVECs) were incubated under hypoxic conditions (1% O(2)) for 48 h. Genome-wide transcript and exon expression levels were assessed using the Affymetrix GeneChip Human Exon 1.0 ST Array. We found altered expression of 294 genes after hypoxia treatment. Upregulated genes are highly enriched in glucose metabolism and angiogenesis related processes, whereas downregulated genes are mainly connected to cell cycle and DNA repair. Thus, gene expression patterns recapitulate known adaptations to low oxygen supply. Alternative splicing events, until now not related to hypoxia, are shown for nine genes: six which are implicated in angiogenesis-mediated cytoskeleton remodeling (cask, itsn1, larp6, sptan1, tpm1 and robo1); one, which is involved in the synthesis of membrane-anchors (pign) and two universal regulators of gene expression (cugbp1 and max).
CONCLUSIONS/SIGNIFICANCE
For the first time, this study investigates changes in splicing in the physiological response to hypoxia on a genome-wide scale. Nine alternative splicing events, until now not related to hypoxia, are reported, considerably expanding the information on splicing changes due to low oxygen supply. Therefore, this study provides further knowledge on hypoxia induced gene expression changes and presents new starting points to study the hypoxia adaptation of endothelial cells.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2012 |
| Autor(en): | Weigand, Julia E. ; Boeckel, Jes-Niels ; Gellert, Pascal ; Dimmeler, Stefanie |
| Art des Eintrags: | Bibliographie |
| Titel: | Hypoxia-induced alternative splicing in endothelial cells |
| Sprache: | Englisch |
| Publikationsjahr: | 2 August 2012 |
| Verlag: | Public Library of Science (PLoS) |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | PloS one |
| Jahrgang/Volume einer Zeitschrift: | 7 |
| (Heft-)Nummer: | 8 |
| DOI: | 10.1371/journal.pone.0042697 |
| URL / URN: | https://journals.plos.org/plosone/article?id=10.1371/journal... |
| Kurzbeschreibung (Abstract): | BACKGROUND Adaptation to low oxygen by changing gene expression is vitally important for cell survival and tissue development. The sprouting of new blood vessels, initiated from endothelial cells, restores the oxygen supply of ischemic tissues. In contrast to the transcriptional response induced by hypoxia, which is mainly mediated by members of the HIF family, there are only few studies investigating alternative splicing events. Therefore, we performed an exon array for the genome-wide analysis of hypoxia-related changes of alternative splicing in endothelial cells. METHODOLOGY/PRINCIPAL FINDINGS Human umbilical vein endothelial cells (HUVECs) were incubated under hypoxic conditions (1% O(2)) for 48 h. Genome-wide transcript and exon expression levels were assessed using the Affymetrix GeneChip Human Exon 1.0 ST Array. We found altered expression of 294 genes after hypoxia treatment. Upregulated genes are highly enriched in glucose metabolism and angiogenesis related processes, whereas downregulated genes are mainly connected to cell cycle and DNA repair. Thus, gene expression patterns recapitulate known adaptations to low oxygen supply. Alternative splicing events, until now not related to hypoxia, are shown for nine genes: six which are implicated in angiogenesis-mediated cytoskeleton remodeling (cask, itsn1, larp6, sptan1, tpm1 and robo1); one, which is involved in the synthesis of membrane-anchors (pign) and two universal regulators of gene expression (cugbp1 and max). CONCLUSIONS/SIGNIFICANCE For the first time, this study investigates changes in splicing in the physiological response to hypoxia on a genome-wide scale. Nine alternative splicing events, until now not related to hypoxia, are reported, considerably expanding the information on splicing changes due to low oxygen supply. Therefore, this study provides further knowledge on hypoxia induced gene expression changes and presents new starting points to study the hypoxia adaptation of endothelial cells. |
| ID-Nummer: | pmid:22876330 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > RNA Biochemie |
| Hinterlegungsdatum: | 05 Mär 2021 07:27 |
| Letzte Änderung: | 05 Mär 2021 07:27 |
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