Dynamic regulation of canonical TGF beta signalling by endothelial transcription factor ERG protects from liver fibrogenesis

The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (ErgcEC-Het) and inducible homozygous deficient mice (ErgiEC-KO), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL4)-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease

Effects of crystallographic orientation on the superelastic response of FeMnAlNi single crystals

The effects of crystal orientation on the tensile superelastic response of the Fe43.5Mn34Al15Ni7.5 single crystalline shape memory alloy, oriented along the and directions were investigated. The single crystals aged at 200 °C for 3 h demonstrated superelastic strains of 3.6% along the orientation and 7.8% along the orientation. Although the theoretical transformation strain in the orientation is higher than that in the orientation, the oriented single crystals demonstrate better superelastic recovery in tension due to a higher number of active martensite variants, which promote better accommodation of internal strains and help minimize defect formation during transformation