Multiple physical stresses induce γ-globin gene expression and fetal hemoglobin production in erythroid cells.

Increased fetal hemoglobin (HbF) expression is beneficial for β-hemoglobinopathy patients; however, current inducing agents do not possess the ideal combination of efficacy, safety and ease of use. Better understanding the mechanisms involved in γ-globin gene induction is critical for designing improved therapies, as no complete mechanism for any inducing agent has been identified. Given the cytotoxic nature of most known inducing drugs, we hypothesized that γ-globin is a cell stress response gene, and that induction occurs via activation of cell stress signaling pathways.

MIF deficiency does not alter glucose homeostasis or adipose tissue inflammatory cell infiltrates during diet-induced obesity.

Objective: Circulating macrophage migration inhibitory factor (MIF) levels have been shown to positively correlate with body mass index (BMI) in humans. Our objective in this study was to determine the effects of MIF deficiency in a model of high-fat diet-induced obesity.

Design And Methods: MIF wild type (MIF WT) and MIF deficient (MIF(-/-)) C57Bl/6J mice were fed a high-fat diet (HFD) for up to 15 weeks.

A cell stress signaling model of fetal hemoglobin induction: what doesn't kill red blood cells may make them stronger.

A major goal of hemoglobinopathy research is to develop treatments that correct the underlying molecular defects responsible for sickle cell disease and beta-thalassemia. One approach to achieving this goal is the pharmacologic induction of fetal hemoglobin (HbF). This strategy is capable of inhibiting the polymerization of sickle hemoglobin and correcting the globin chain imbalance of beta-thalassemia.

Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin.

5-azacytidine (5-Aza) is a potent inducer of fetal hemoglobin (HbF) in people with beta-thalassemia and sickle cell disease. Two models have been proposed to explain this activity. The first is based on the drug's ability to inhibit global DNA methylation, including the fetal globin genes, resulting in their activation.