RESUMEN
The cutaneous response to injury and stress comprises a temporary change in the balance between epidermal proliferation and differentiation as well as an activation of the immune system. Soluble factors play an important role in the regulation of these complex processes by coordinating the intercellular communication between keratinocytes, fibroblasts, and inflammatory cells. In this study, we demonstrate that JunB, a member of the activator protein-1 transcription factor family, is an important regulator of cytokine expression and thus critically involved in the cutaneous response to injury and stress. Mice lacking JunB in the skin develop normally, indicating that JunB is neither required for cutaneous organogenesis, nor homeostasis. However, upon wounding and treatment with the phorbol ester 12-O-decanoyl-phorbol-13-acetate, JunB-deficiency in the skin likewise resulted in pronounced epidermal hyperproliferation, disturbed differentiation, and prolonged inflammation. Furthermore, delayed tissue remodelling was observed during wound healing. These phenotypic skin abnormalities were associated with JunB-dependent alterations in expression levels and kinetics of important mediators of wound repair, such as granulocyte macrophage colony-stimulating factor, growth-regulated protein-1, macrophage inflammatory protein-2, and lipocalin-2 in both the dermal and epidermal compartment of the skin, and a reduced ability of wound contraction of mutant dermal fibroblasts in vitro.
Asunto(s)
Citocinas/metabolismo , Epidermis/fisiología , Ratones Noqueados/genética , Proteínas Proto-Oncogénicas c-jun/genética , Cicatrización de Heridas/genética , Animales , Proliferación Celular , Colágeno/genética , Colágeno Tipo I , Citocinas/genética , Epidermis/efectos de los fármacos , Epidermis/embriología , Genes Letales , Homeostasis/genética , Integrasas/metabolismo , Ratones , Recombinación Genética , Eliminación de Secuencia , Piel/citología , Piel/efectos de los fármacos , Piel/embriología , Acetato de Tetradecanoilforbol/toxicidad , Proteínas Virales/metabolismo , Cicatrización de Heridas/inmunologíaRESUMEN
Preeclampsia is a multisystemic pregnancy-associated disease affecting about 3-7% of pregnancies worldwide and is still a principal cause of fetal and maternal morbidity and mortality. To identify potential markers, we have compared gene expression profiles from control and preeclamptic placental tissues taken at various age-matched gestational stages using complementary DNA microarray analysis. Besides previously identified preeclampsia-associated genes, novel differentially expressed transcripts were found. The soluble form of the disintegrin metalloprotease ADAM 12 (a disintegrin and metalloproteinase 12; meltrin-alpha) represented the most upregulated transcript. This was confirmed by in situ hybridization of sections of preeclamptic placentas and by serum protein analysis of preeclamptic pregnant women. Thus, ADAM 12 could serve as an early biomarker for preeclampsia that may be of predictive and/or functional significance.
Asunto(s)
Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Placenta/metabolismo , Preeclampsia/diagnóstico , Preeclampsia/metabolismo , Proteínas ADAM/sangre , Proteína ADAM12 , Adulto , Biomarcadores/sangre , Biomarcadores/metabolismo , Vellosidades Coriónicas/metabolismo , Femenino , Perfilación de la Expresión Génica , Edad Gestacional , Humanos , Hibridación in Situ , Proteínas de la Membrana/sangre , Análisis de Secuencia por Matrices de Oligonucleótidos , Placenta/química , Placenta/patología , Preeclampsia/patología , Embarazo , ARN Mensajero/metabolismo , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia ArribaRESUMEN
A 105 kb Fugu rubripes genomic region containing the RUNX2 ortholog (frunx2) was sequenced and analysed. Spanning 32 kb, frunx2 is seven times smaller than its human orthologue (223 kb). By comparison of Fugu and human genomic environment a stretch of conserved synteny, comprising the neighbouring genes on both sides, was identified. Except one exon that is alternatively spliced in human RUNX2, all other seven exons could be identified in frunx2. The predicted protein sequence of frunx2 shows a high degree of sequence conservation compared with RUNX2 (83% identity). Like all human paralogues, frunx2 possesses two promoter regions separated by a large intron. Both promoter regions are conserved between the two species and contain several RUNX binding sites pointing to a self-regulatory function. Three further conserved non-coding regions were identified possibly functioning as enhancer elements for tissue-specific expression of RUNX2.
