| Texto completo | |
| Autor(es): Mostrar menos - |
Rodrigues, Bruno Lima
;
Pascoal, Livia Bitencourt
;
Genaro, Livia Moreira
;
Warrak, Leonardo Saint Clair Assad
;
Rodrigues, Beatriz Alves Guerra
;
Coope, Andressa
;
Camargo, Michel Gardere
;
Oliveira, Priscilla de Sene Portel
;
Ayrizono, Maria de Lourdes Setsuko
;
Velloso, Licio Augusto
;
Leal, Raquel Franco
Número total de Autores: 11
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| Tipo de documento: | Artigo Científico |
| Fonte: | CELLS; v. 14, n. 4, p. 16-pg., 2025-02-01. |
| Resumo | |
Background: Crohn's disease (CD) is an inflammatory bowel disease marked by an abnormal immune response and excessive pro-inflammatory cytokines, leading to impaired protein processing and endoplasmic reticulum (ER) stress. This stress, caused by the accumulation of misfolded proteins, triggers the unfolded protein response (UPR) through IRE1/Xbp-1, PERK/eIF2 alpha, and ATF6 pathways, which are linked to intestinal inflammation. This study aimed to investigate ER stress in CD patients' intestinal mucosa and evaluate phenylbutyrate (PBA) as an ER stress inhibitor. Methods: Colon biopsies from CD patients and controls were cultured under five conditions, including 4-PBA treatments. Real-time PCR, cytokine level, and immunohistochemistry were performed. Results: Immunohistochemistry revealed that ER stress was activated in CD patients' intestinal epithelial cells and lamina propria cells. PERK/eIF2 alpha, but not IRE1/Xbp-1 or ATF6, was upregulated in CD patients compared to controls. UPR-related genes (STC2, CALR, HSPA5, HSP90B1) were also elevated in CD patients. PBA treatment significantly reduced ER stress and UPR markers while decreasing apoptotic markers like DDIT3. Pro-inflammatory cytokines, such as IL-1 beta, IL-6, IL-17, TNF- alpha, and sCD40L, were significantly reduced after PBA treatment. Conclusion: ER stress and UPR pathways are activated in CD colonic mucosa, and PBA reduces these markers, suggesting potential therapeutic benefits for CD-related inflammation. (AU) | |
| Processo FAPESP: | 20/01924-5 - Avaliação dos níveis plasmáticos de Adalimumabe e detecção de anticorpos anti-Adalimumabe em pacientes com Doença de Crohn |
| Beneficiário: | Livia Moreira Genaro |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 20/04407-1 - Avaliação e inibição do estresse de retículo endoplasmático na mucosa intestinal de pacientes com doença de Crohn |
| Beneficiário: | Raquel Franco Leal |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |