Web of Science: 3 cites, Scopus: 4 cites, Google Scholar: cites,
Decreased TESK1-mediated cofilin 1 phosphorylation in the jejunum of IBS-D patients may explain increased female predisposition to epithelial dysfunction
Rodiño-Janeiro, Bruno K. (Vall d'Hebron Institut de Recerca)
Martínez, Cristina (Vall d'Hebron Institut de Recerca)
Fortea, Marina (Vall d'Hebron Institut de Recerca)
Lobo Álvarez, Beatriz (Vall d'Hebron Institut de Recerca)
Pigrau Pastor, Marc (Vall d'Hebron Institut de Recerca)
Nieto, Adoración (Vall d'Hebron Institut de Recerca)
González-Castro, Ana María (Vall d'Hebron Institut de Recerca)
Salvo Romero, Eloísa (Vall d'Hebron Institut de Recerca)
Guagnozzi, Danila (Vall d'Hebron Institut de Recerca)
Pardo-Camacho, Cristina (Vall d'Hebron Institut de Recerca)
Iribarren, Cristina (Vall d'Hebron Institut de Recerca)
Azpiroz Vidaur, Fernando (Vall d'Hebron Institut de Recerca)
Alonso Cotoner, Carmen (Vall d'Hebron Institut de Recerca)
Santos, Javier (Vall d'Hebron Institut de Recerca)
Vicario Pérez, María (Vall d'Hebron Institut de Recerca)

Data: 2018
Resum: Disturbed intestinal epithelial barrier and mucosal micro-inflammation characterize irritable bowel syndrome (IBS). Despite intensive research demonstrating ovarian hormones modulation of IBS severity, there is still limited knowledge on the mechanisms underlying female predominance in this disorder. Our aim was to identify molecular pathways involved in epithelial barrier dysfunction and female predominance in diarrhea-predominant IBS (IBS-D) patients. Total RNA and protein were obtained from jejunal mucosal biopsies from healthy controls and IBS-D patients meeting the Rome III criteria. IBS severity was recorded based on validated questionnaires. Gene and protein expression profiles were obtained and data integrated to explore biological and molecular functions. Results were validated by western blot. Tight junction signaling, mitochondrial dysfunction, regulation of actin-based motility by Rho, and cytoskeleton signaling were differentially expressed in IBSD. Decreased TESK1-dependent cofilin 1 phosphorylation (pCFL1) was confirmed in IBS-D, which negatively correlated with bowel movements only in female participants. In conclusion, deregulation of cytoskeleton dynamics through TESK1/CFL1 pathway underlies epithelial intestinal dysfunction in the small bowel mucosa of IBS-D, particularly in female patients. Further understanding of the mechanisms involving sex-mediated regulation of mucosal epithelial integrity may have significant preventive, diagnostic, and therapeutic implications for IBS.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Publicat a: Scientific reports, Vol. 8 (2018) , art. 2255, ISSN 2045-2322

DOI: 10.1038/s41598-018-20540-9
PMID: 29396473

11 p, 2.3 MB

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