Dengler, F.; Sova, S.; Salo, A.M.; Mäki, J.M.; Koivunen, P.; Myllyharju, J. Expression and Roles of Individual HIF Prolyl 4-Hydroxylase Isoenzymes in the Regulation of the Hypoxia Response Pathway along the Murine Gastrointestinal Epithelium. Int. J. Mol. Sci. 2021, 22, 4038. https://doi.org/10.3390/ijms22084038
Expression and roles of individual HIF prolyl 4-hydroxylase isoenzymes in the regulation of the hypoxia response pathway along the murine gastrointestinal epithelium
|Author:||Dengler, Franziska1,2,3; Sova, Sofia2; Salo, Antti M.2;|
1Unit of Physiology, Pathophysiology and Experimental Endocrinology, University of Veterinary Medicine, 1210 Vienna, Austria
2Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90220 Oulu, Finland
3Institute of Veterinary Physiology, University of Leipzig, 04103 Leipzig, Germany
|Online Access:||PDF Full Text (PDF, 1.4 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021070741216
Multidisciplinary Digital Publishing Institute,
|Publish Date:|| 2021-07-07
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.
International journal of molecular sciences
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This study was supported by an EMBO short-term fellowship and a FEBS fellowship (FD), Academy of Finland Grants 296498 (JM) and 308009 (PK), Sigrid Jusélius Foundation Grants (JM, PK) and Jane and Aatos Erkko Foundation Grant (JM, PK).
|Academy of Finland Grant Number:||
296498 (Academy of Finland Funding decision)
308009 (Academy of Finland Funding decision)
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