An Elf2-like transcription factor acts as repressor of the mouse ecto-5'-nucleotidase gene expression in hepatic myofibroblasts

Hepatic fibrosis represents a pathological wound healing and tissue repair process triggered in response to chronic liver injury. A heterogeneous population of activated non-parenchymal liver cells, known as liver myofibroblasts, functions as the effector cells in hepatic fibrosis. Upon activation, liver myofibroblasts become fibrogenic, acquiring contractile properties and increasing collagen production capacity, while developing enhanced sensitivity to endogenous molecules and factors released in the local microenvironment. Hepatic extracellular adenosine is a bioactive small molecule, increasingly recognized as an important regulator of liver myofibroblast functions, and an important mediator in the pathogenesis of liver fibrosis overall. Remarkably, ecto-5'-nucleotidase/Nt5e/Cd73 enzyme, which accounts for the dominant adenosine-generating activity in the extracellular medium, is expressed by activated liver myofibroblasts. However, the molecular signals regulating Nt5e gene expression in liver myofibroblasts remain poorly understood. Here, we show that activated mouse liver myofibroblasts express Nt5e gene products and characterize the putative Nt5e minimal promoter in the mouse species. We describe the existence of an enhancer sequence upstream of the mouse Nt5e minimal promoter and establish that the mouse Nt5e minimal promoter transcriptional activity is negatively regulated by an Elf2-like Ets-related transcription factor in activated mouse liver myofibroblasts.

Medienart:

E-Artikel

Erscheinungsjahr:

2017

Erschienen:

2017

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Purinergic signalling - 13(2017), 4 vom: 01. Dez., Seite 417-428

Sprache:

Englisch

Beteiligte Personen:

Fausther, Michel [VerfasserIn]
Lavoie, Elise G [VerfasserIn]
Goree, Jessica R [VerfasserIn]
Dranoff, Jonathan A [VerfasserIn]

Links:

Volltext

Themen:

5'-Nucleotidase
Adenosine
Cloning
Cluster of differentiation 73 (Cd73)
DNA-Binding Proteins
E74-like factor 2/new ETS-related factor (Elf2/Nerf)
EC 3.1.3.5
ETS transcription factor family
Ecto-5′-nucleotidase (Nt5e)
Electric mobility shift assay
Elf2 protein, mouse
Journal Article
Promoter
Surface enzyme
Transcription Factors
Transcriptional regulation

Anmerkungen:

Date Completed 27.07.2018

Date Revised 30.12.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s11302-017-9570-7

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM27344655X