Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Πέμπτη 24 Δεκεμβρίου 2015

Farnesoid X Receptor-dependent and -independent Pathways Mediate the Transcriptional Control of Human Fibroblast Growth Factor 19 by Vitamin A

Publication date: Available online 23 December 2015
Source:Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms
Author(s): Daniel Jahn, Dominic Sutor, Donata Dorbath, Johannes Weiß, Oliver Götze, Johannes Schmitt, Heike M. Hermanns, Andreas Geier
Fibroblast growth factor 19 (FGF19) is a gut-derived hormone that controls bile acid (BA), carbohydrate and lipid metabolism. Whereas strong evidence supports a key role of BAs and farnesoid X receptor (FXR) for the control of FGF19 expression, information on other regulators is limited. In mice, FGF15 expression (ortholog of human FGF19) is induced by vitamin A (VitA) in an FXR-dependent manner. However, the significance of this finding for human FGF19 is currently unclear. Here, we demonstrate that VitA derivatives induce FGF19 in human intestinal cell lines by a direct transcriptional mechanism. In contrast to mouse FGF15, however, this direct regulation is not dependent on FXR but mediated by retinoic acid receptors (RAR) and their interaction with a novel DR-5 element in the human FGF19 gene. In addition to this direct effect, VitA derivatives impacted on the BA-mediated control of FGF19 by regulation of FXR protein levels. In conclusion, VitA regulates human FGF19 expression through FXR-dependent and -independent pathways. Moreover, we suggest that considerable mechanistic differences exist between humans and mice with regard to the nuclear receptors controlling the VitA-FGF15/19 axis. These findings may implicate a clinical relevance of RAR-activating VitA derivatives for the regulation of FGF19 levels in humans.

Graphical abstract

image

from #Medicine-SfakianakisAlexandros via o.lakala70 on Inoreader http://ift.tt/1RIkwBB
via IFTTT

from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1OptSSq
via IFTTT



from #Med Blogs by Alexandros G.Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1RIqrqr
via IFTTT

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Αρχειοθήκη ιστολογίου