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We have identified integrin beta 6 ( Itgb6) as a transcript highly enriched in skeletal muscle. This finding is unexpected because Itgb6 is typically associated with epithelial expression domains in normal tissue. Further we find that ITGB6 protein expression in muscle is post-transcriptionally regulated. Uninjured muscle expresses Itgb6 RNA but no ITGB6 protein is detectable. Muscle injury induces ITGB6 protein accumulation rapidly post-injury in myofibers adjacent to the site of injury. As regeneration of the injured muscle tissue progresses ITGB6 protein is found in newly formed fibers up to at least 15 days post-injury. [ABSTRACT FROM AUTHOR]

Abstract. Objective:  To define the anti-inflammatory effects of PPARβ/δ activation by use of the selective PPARβ/δ ligand (GW0742) in a model of lipopolysaccharide (LPS)-induced pulmonary inflammation. Methods:  Male BALB/c mice were pretreated for three days with the PPARβ/δ agonist, GW0742, prior to induction of LPS-mediated pulmonary inflammation. Bronchial alveolar lavage fluid (BALF) was analyzed for inflammatory cell influx and for levels of pro-inflammatory mediators. BALF-derived inflammatory cells were also collected for mRNA analysis. Results:  Pretreatment with GW0742 resulted in a significant decrease in leukocyte recruitment into the pulmonary space. Protein and mRNA levels of the pro-inflammatory cytokines IL-6, IL-1β and TNFα in BALF were found to be significantly decreased in GW0742-treated animals (30 mg/kg). A significant decrease in granulocyte macrophage-colony stimulating factor (GM-CSF), a major regulator of neutrophil chemotaxis (via its downstream actions on TNFα and other cytokines/chemokines), activation and survival, was also noted in the BALF levels of GW0742-treated animals. Conclusions:  The present study demonstrates that activation of PPARβ/δ attenuates the degree of inflammation in a model of LPS-induced pulmonary inflammation and may therefore represent a novel therapeutic approach for the treatment of inflammation-mediated pathologies. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR-delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor (PPAR) β-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPARβ will inhibit keratinocyte proliferation. By using of a highly specific ligand (GW0742) and the PPARβ-null mouse model, activation of PPARβ was found to selectively induce keratinocyte terminal differentiation and inhibit keratinocyte proliferation. Additionally, GW0742 was found to be anti-inflammatory due to inhibition of myeloperoxidase activity, independent of PPARβ. These data suggest that ligand activation of PPARβ could be a novel approach to selectively induce differentiation and inhibit cell proliferation, thus representing a new molecular target for the treatment of skin disorders resulting from altered cell proliferation such as psoriasis and cancer.Cell Death and Differentiation (2006) 13, 53–60. doi:10.1038/sj.cdd.4401713; published online 15 July 2005 [ABSTRACT FROM AUTHOR]

The Cbf5 protein of Saccharomyces cerevisiae was originally identified as a low-affinity centromeric DNA-binding protein, and cbf5 mutants have a defect in rRNA synthesis. A closely related protein from mammals, NAP57, is a nucleolar protein that coimmunoprecipitates with the nucleolar phosphoprotein Nopp140. To study the function of this protein family in a higher eukaryote that is amenable to genetic approaches, the gene encoding a Drosophilamelanogaster homolog, Nop60B, was identified. The predicted Drosophila protein shares a high degree of sequence identity over a 380-residue region with both the mammalian and yeast proteins, and shares several conserved motifs with the prokaryotic tRNA pseudouridine 55 synthases. Nop60B RNA is found at high levels in nurse cells and in the oocyte, and is present throughout development. Nop60B protein is localized primarily to the nucleolus of interphase cells, and is absent from the chromosomes during mitosis. Nop60B mutants were generated and shown to be homozygous lethal. The Drosophila gene can rescue the lethal phenotype of yeast cbf5 mutations, showing that the function of this protein has been conserved from yeast to Drosophila. [ABSTRACT FROM AUTHOR]

We have used antibodies directed against a unique portion of the Drosophila POU domain protein Cfla to localize its sites of expression in developing embryos. Cfla protein is first detected during germ band extension in the tracheal placodes and in the midline mesectoderm cells. Tracheal expression continues throughout embryonic development, especially in the main longitudinal tracheal trunks. Additional sites of high Cfla expression are in the anterior portion of the hindgut, the roof of the stomodeum, a subset of central nervous system cells, the oenocytes, and the ring gland. In addition, Cfla expression was localized in embryos mutant for several loci involved in determining fate along the midline of the CNS and the tracheal system. Cfla midline cell expression is dependent on proper single-minded gene function, and Cfla either regulates or acts in parallel to the genes pointed and rhomboid during midline CNS and tracheal development. [ABSTRACT FROM AUTHOR]