The E2F6 Transcription Factor is Associated with the Mammalian SUZ12-Containing Polycomb Complex.

The Polycomb group protein (PcG) SUZ12 forms Polycomb repressive complexes together with histone methyltransferase EZH2. Although the complexes have been demonstrated to be involved in epigenetic maintenance of gene expression in a transcriptional repressive state, it is unclear how they are recruited to the target genes. Here we report that SUZ12 directly interacts with site-specific transcriptional repressor E2F6 and forms a complex together with EZH2.

Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout.

Objective: The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout.

Methods: We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed.

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

Objective: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific.

Methods: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes.

Dual effect of AMD3100, a CXCR4 antagonist, on bleomycin-induced lung inflammation.

The chemokine receptor CXCR4, which binds the chemokine stromal cell-derived factor 1, has been reported to be involved in the chemotaxis of inflammatory cells. In addition, AMD3100, an antagonist of CXCR4, has been reported to be an attractive drug candidate for therapeutic intervention in several disorders in which CXCR4 is critically involved. However, little is known about the therapeutic value of AMD3100 in the treatment of pulmonary fibrosis.

Increased expression of TRAIL receptor 3 on eosinophils in Churg-Strauss syndrome.

Objective: Prolonged survival of eosinophils plays an important role in the pathogenesis of Churg-Strauss syndrome (CSS); however, its detailed molecular mechanism is still unclear. TRAIL and its receptors are expressed on a variety of cells, including eosinophils. In this study, we examined the expression of TRAIL receptors on eosinophils from patients with CSS.

Discoidin domain receptor 1 contributes to eosinophil survival in an NF-kappaB-dependent manner in Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) is a systemic disease that shows marked eosinophilia along with eosinophil infiltration in the tissue. Prolonged eosinophil survival plays an important role in the pathogenesis of CSS; however, its detailed molecular mechanism remains unclear. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase, and its ligand is collagen.

Discoidin domain receptor 1 contributes to the survival of lung fibroblast in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF), characterized by fibroblast proliferation and accumulation of extracellular matrix, including collagen, is a chronic progressive disorder that results in lung remodeling and fibrosis. However, the cellular mechanisms that may make fibroblasts resistant to apoptosis have not been completely elucidated. Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase whose ligand is collagen, is expressed in vivo and contributes in vitro to leukocyte differentiation and nuclear factor (NF)-kappaB activation, which may play an important role in fibroblast survival.

Suppression of discoidin domain receptor 1 by RNA interference attenuates lung inflammation.

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase whose ligand is collagen. Recently, we have reported the association of DDR1 in the cytokine production of human leukocytes in in vitro and in vivo expression in idiopathic pulmonary fibrosis. However, its role in in vivo inflammation has not been fully elucidated.

Desert hedgehog-patched 2 expression in peripheral nerves during Wallerian degeneration and regeneration.

Hedgehog proteins are important in the development of the nervous system. As Desert hedgehog (Dhh) is involved in the development of peripheral nerves and is expressed in adult nerves, it may play a role in the maintenance of adult nerves and degeneration and regeneration after injury. We firstly investigated the Dhh-receptors, which are expressed in mouse adult nerves.

Involvement of discoidin domain receptor 1 in the deterioration of pulmonary sarcoidosis.

The prognosis of sarcoidosis with pulmonary infiltrates differs in each case, and several cytokines are reported to contribute to its deterioration. However, the detailed mechanism has not been fully elucidated. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen and associated with cytokine production from inflammatory cells.

Activation of discoidin domain receptor 1 on CD14-positive bronchoalveolar lavage fluid cells induces chemokine production in idiopathic pulmonary fibrosis.

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by collagen. We previously reported the functional expression of DDR1 on human monocyte-derived macrophages in vitro; however, information regarding its role in diseases is limited. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease, and the lesions contain an abundance of collagen.