Expression and roles of individual HIF prolyl 4-hydroxylase isoenzymes in the regulation of the hypoxia response pathway along the murine gastrointestinal epithelium
| Autor: | Johanna Myllyharju, Peppi Koivunen, Sofia Sova, Antti M. Salo, Joni M. Mäki, Franziska Dengler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Aging mRNA ddPCR Biology Gastrointestinal epithelium Gene Expression Regulation Enzymologic Article Catalysis Hypoxia-Inducible Factor-Proline Dioxygenases lcsh:Chemistry Inorganic Chemistry caecum 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Gene expression medicine Animals HIF RNA Messenger Intestinal Mucosa Physical and Theoretical Chemistry jejunum Hypoxia Cecum lcsh:QH301-705.5 Molecular Biology Spectroscopy 030304 developmental biology 0303 health sciences Gastrointestinal tract colon Organic Chemistry General Medicine Epithelium Computer Science Applications Cell biology Gut Epithelium HIF-prolyl 4-hydroxylase Isoenzymes Mice Inbred C57BL medicine.anatomical_structure HIF1A lcsh:Biology (General) lcsh:QD1-999 epithelium 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 8 International Journal of Molecular Sciences, Vol 22, Iss 4038, p 4038 (2021) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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