{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:21:36Z","timestamp":1774462896614,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","award":["7675"],"award-info":[{"award-number":["7675"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012623","name":"Federation of European Biochemical Societies","doi-asserted-by":"publisher","award":["fellowship"],"award-info":[{"award-number":["fellowship"]}],"id":[{"id":"10.13039\/100012623","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["296498"],"award-info":[{"award-number":["296498"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["308009"],"award-info":[{"award-number":["308009"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane ja Aatos Erkon S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u201cphysiological hypoxia\u201d 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\u2212\/\u2212, Hif-p4h-2 hypomorph and Hif-p4h-3\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/ijms22084038","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T15:30:39Z","timestamp":1618414239000},"page":"4038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expression and Roles of Individual HIF Prolyl 4-Hydroxylase Isoenzymes in the Regulation of the Hypoxia Response Pathway along the Murine Gastrointestinal Epithelium"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2178-2270","authenticated-orcid":false,"given":"Franziska","family":"Dengler","sequence":"first","affiliation":[{"name":"Unit of Physiology, Pathophysiology and Experimental Endocrinology, University of Veterinary Medicine, 1210 Vienna, Austria"},{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90220 Oulu, Finland"},{"name":"Institute of Veterinary Physiology, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5452-7922","authenticated-orcid":false,"given":"Sofia","family":"Sova","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90220 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antti M.","family":"Salo","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90220 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joni M.","family":"M\u00e4ki","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90220 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peppi","family":"Koivunen","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90220 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Myllyharju","sequence":"additional","affiliation":[{"name":"Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, 90220 Oulu, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cell.2012.01.021","article-title":"Hypoxia-inducible factors in physiology and medicine","volume":"148","author":"Semenza","year":"2012","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1515\/hsz-2012-0328","article-title":"Hypoxia-inducible factor prolyl 4-hydroxylases: Common and specific roles","volume":"394","author":"Myllyharju","year":"2013","journal-title":"Biol. 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