RESUMO
Epithelial-repair-dependent mucosal healing (MH) is associated with a more favorable prognosis for patients with inflammatory bowel disease (IBD). MH is accomplished via repair and regeneration of the intestinal epithelium. However, the mechanism underlying MH is ill defined. We found a striking upregulation of peroxisomes in the injured crypts of IBD patients. By increasing peroxisome levels in Drosophila midguts, we found that peroxisome elevation enhanced RAB7-dependent late endosome maturation, which then promoted stem and/or progenitor-cell differentiation via modulation of Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT)-SOX21A signaling. This in turn enhanced ISC-mediated regeneration. Importantly, RAB7 and SOX21 were upregulated in the crypts of IBD patients. Moreover, administration of drugs that increased peroxisome levels reversed the symptoms of dextran sulfate sodium (DSS)-induced colitis in mice. This study demonstrates a peroxisome-mediated epithelial repair mechanism, which opens a therapeutic avenue for the enhancement of MH in IBD patients.
Assuntos
Diferenciação Celular , Neoplasias Colorretais/patologia , Regulação da Expressão Gênica , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/citologia , Peroxissomos/fisiologia , Células-Tronco/citologia , Adolescente , Adulto , Animais , Neoplasias Colorretais/metabolismo , Drosophila melanogaster , Feminino , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Janus Quinases/genética , Janus Quinases/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fatores de Transcrição SOXB2/genética , Fatores de Transcrição SOXB2/metabolismo , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Adulto Jovem , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , proteínas de unión al GTP Rab7RESUMO
The complete chloroplast genome of Ziziphus jujuba cv. dongzao, known as an important economic cultivar in Yellow River Delta of China was reported. It exhibits a quadripartite structure with 161,493 bp including a large single copy region (89,178 bp), a small single copy region (19,357 bp) and a pair of inverted repeats regions (26,479 bp). It has 36.79% GC content and 114 unique genes. Phylogenetic analysis showed that it was a member of Ziziphus and more closely related to Berchemiella wilsonii. Border analysis revealed that there were some differences in the borders of the four related cultivars.
