The loss of α2β1 integrin suppresses joint inflammation and cartilage destruction in mouse models of rheumatoid arthritis.

Objective: Integrin α2β1 functions as a major receptor for type I collagen on different cell types, including fibroblasts and inflammatory cells. Although in vitro data suggest a role for α2β1 integrin in regulating both cell attachment and expression of matrix-degrading enzymes such as matrix metalloproteinases (MMPs), mice that lack the α2 integrin subunit (Itga2(-/-) mice) develop normally and are fertile. We undertook this study to investigate the effect of Itga2 deficiency in 2 different mouse models of destructive arthritis: the antigen-induced arthritis (AIA) mouse model and the human tumor necrosis factor α (TNFα)-transgenic mouse model.

Establishment of a matrix-associated transepithelial resistance invasion assay to precisely measure the invasive potential of synovial fibroblasts.

Objective: Synovial fibroblasts (SFs) contribute to several aspects of the pathogenesis of rheumatoid arthritis (RA) and have been implicated most prominently in the progressive destruction of articular cartilage. Targeting the invasive phenotype of RASFs has therefore gained increasing attention, but the precise measurement of their invasive capacity and the evaluation of potential treatment effects constitute a challenge that needs to be addressed. This study used a novel in vitro invasion assay based on the breakdown of transepithelial electrical resistance to determine the course of fibroblast invasion into extracellular matrix.

ProSAP-interacting protein 1 (ProSAPiP1), a novel protein of the postsynaptic density that links the spine-associated Rap-Gap (SPAR) to the scaffolding protein ProSAP2/Shank3.

ProSAPs/Shanks are a family of proteins that have a major scaffolding function for components of the postsynaptic density (PSD) of excitatory brain synapses. Members of the family harbor a variety of domains for protein-protein interactions, one of which is a unique PDZ domain that differs significantly from those of other proteins. We have identified a novel binding partner for this PDZ domain, termed ProSAPiP1, that is highly enriched in the PSD and shares significant sequence homology with the PSD protein PSD-Zip70.

Bradykinin-induced pulmonary vasoconstriction is time and inducible nitric oxide synthase dependent in a peritonitis sepsis model.

In an isolated perfused lung model, bradykinin induced pulmonary vasoconstriction in rats made septic by the injection of lipopolysaccharide (LPS). To mimic the pathophysiology of sepsis in humans more closely, we investigated pulmonary endothelial injury in a peritonitis model (cecal ligation and perforation; CLP). Male Sprague-Dawley rats were randomly divided into nine groups (n = 6-8).

Brain-specific splicing of alpha-actinin 1 (ACTN1) mRNA.

Two isoforms of alpha-actinin 1 (ACTN1) known to be generated by tissue-specific alternative splicing of mutually exclusive exons have been described. Muscle cells express ACTN1 containing the smooth muscle exon (SM), while other (non-muscle) cells contain the non-muscle exon (NM). In this report, we describe the characterization of a novel ACTN1 isoform in adult rat brain in which both exons (NM + SM) are combined in the same transcript to give a brain-specific sequence domain (BS).

Insulin-induced expression of the activity-regulated cytoskeleton-associated gene (ARC) in human neuroblastoma cells requires p21(ras), mitogen-activated protein kinase/extracellular regulated kinase and src tyrosine kinases but is protein kinase C-independent.

We examined the effect of insulin on the expression of the activity-regulated cytoskeleton-associated gene (ARC), an effector immediate early gene with a proposed role in memory formation. In human SH-SY5Y neuroblastoma cells, application of insulin leads to dramatic increase in ARC mRNA and protein levels. Inhibition experiments reveal, that p21(ras), mitogen-activated protein kinase/extracellular regulated kinase and tyrosine kinase (src) activity are required for the insulin-induced ARC expression in SH-SY5Y cells, whereas protein kinase C is not involved in the signal transduction pathway.