RESUMEN
BACKGROUND AND AIMS: Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT. METHODS: Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis. RESULTS: High levels of TL1A expression were detected in the intestinal specimens of patients with ulcerative colitis and Crohn's disease and were negatively associated with the expression of an epithelial marker (E-cadherin), while it was positively associated with the expression of interstitial markers (FSP1 and α-SMA). Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis. Additionally, the TGF-ß1/Smad3 pathway may be involved in TL1A-induced EMT, and the expression of IL-13 and EMT-related transcriptional molecules (e.g., ZEB1 and Snail1) was increased in the intestinal specimens of the transgenic mice. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 in vitro. CONCLUSIONS: TL1A participates in the formation and process of EMT in intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment.
Asunto(s)
Colitis/metabolismo , Transición Epitelial-Mesenquimal , Fibrosis/metabolismo , Intestinos/metabolismo , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Adulto , Animales , Proteína Morfogenética Ósea 7/metabolismo , Cadherinas/metabolismo , Enfermedad Crónica , Femenino , Células HT29 , Humanos , Sistema Inmunológico , Inflamación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
This study investigated the genetic diversity of morchella species using randomly amplified polymorphic DNA markers. Morchella species are an important group of edible mushrooms belonging to the family Helveliaceae with medicinal and economical significance. In this study we have developed an efficient method of genomic DNA isolation which was amplified by eight RAPD primers to test the polymorphism in three species of morchella. Out of all eight primers tested in current study, one of them (B8) resulted 100% polymorphism among the three studied species. Based on the RAPD profile a similarity matrix was generated to construct a dendrogram for phylogenetic analysis revealing the relationship among the three species of morchella.