The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful
mechanism regulating cellular adaptation to decreased oxygenation. The gastrointestinal epithelium
subsists in “physiological hypoxia” and should therefore have an especially well-designed
control over this adaptation. Thus, we assessed the absolute mRNA expression levels of the HIF
pathway components, Hif1a, HIF2a, Hif-p4h-1, 2 and 3 and factor inhibiting HIF (Fih1) in murine
jejunum, caecum and colon epithelium using droplet digital PCR.We found a higher expression of
all these genes towards the distal end of the gastrointestinal tract. We detected mRNA for Hif-p4h-1,
2 and 3 in all parts of the gastrointestinal tract. Hif-p4h-2 had significantly higher expression levels
compared to Hif-p4h-1 and 3 in colon and caecum epithelium. To test the roles each HIF-P4H
isoform plays in the gut epithelium, we measured the gene expression of classical HIF target genes
in Hif-p4h-1/, Hif-p4h-2 hypomorph and Hif-p4h-3/ mice. Only Hif-p4h-2 hypomorphism led
to an upregulation of HIF target genes, confirming a predominant role of HIF-P4H-2. However,
the abundance of Hif-p4h-1 and 3 expression in the gastrointestinal epithelium implies that these
isoforms may have specific functions as well. Thus, the development of selective inhibitors might be
useful for diverging therapeutic needs.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89422 |
| Date | 30 January 2024 |
| Creators | Dengler, Franziska, Sova, Sofia, Salo, Antti M., Mäki, Joni M., Koivunen, Peppi, Myllyharju, Johanna |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 4038 |
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