The integrin PSI domain has an endogenous thiol isomerase function and is a novel target for antiplatelet therapy.

Integrins are a large family of heterodimeric transmembrane receptors differentially expressed on almost all metazoan cells. Integrin β subunits contain a highly conserved plexin-semaphorin-integrin (PSI) domain. The CXXC motif, the active site of the protein-disulfide-isomerase (PDI) family, is expressed twice in this domain of all integrins across species.

New insights into Shiga toxin-mediated endothelial dysfunction in hemolytic uremic syndrome.

Shiga toxin-producing E. coli represents a significant global health concern, especially as hypervirulent pathogens surface amidst outbreaks of hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is key in the microangiopathic events underlying the disease and its central role is underscored by the unprecedented HUS outbreak in Germany in 2011.

Dysregulation of angiopoietin 1 and 2 in Escherichia coli O157:H7 infection and the hemolytic-uremic syndrome.

Escherichia coli O157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormalities. Endothelial dysfunction, manifested as dysregulation of angiopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology. We measured Ang-1/2 in 77 children with E.

Functional importance of Dicer protein in the adaptive cellular response to hypoxia.

The processes by which cells sense and respond to ambient oxygen concentration are fundamental to cell survival and function, and they commonly target gene regulatory events. To date, however, little is known about the link between the microRNA pathway and hypoxia signaling. Here, we show in vitro and in vivo that chronic hypoxia impairs Dicer (DICER1) expression and activity, resulting in global consequences on microRNA biogenesis.

Shiga toxin-associated hemolytic uremic syndrome: advances in pathogenesis and therapeutics.

Purpose Of Review: Diarrhea-associated hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) continues to be an important public health threat worldwide. Specific therapies are lacking and patient care remains largely supportive. This review discusses the lessons learned from recent events and summarizes key advances made toward understanding the basic mechanisms involved in the pathogenesis of typical HUS.

The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice.

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury.