Percorrer por autor "Gullo, Irene"
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- Fibrosis-related transcriptome unveils a distinctive remodelling matrix pattern in penetrating ileal Crohn’s diseasePublication . Sousa, Helena Tavares; Ferreira, Marta; Gullo, Irene; Rocha, Ana Mafalda; Pedro, Ana; Leitão, Dina; Oliveira, Carla; Carneiro, Fátima; Magro, FernandoBackground and Aims: Stricturing [B2] and penetrating [B3] ileal Crohn’s disease have been reported to present similar levels of histopathological transmural fibrosis. This study aimed to compare the fibrosis-related transcriptomic profiles of penetrating and stricturing ileal Crohn’s disease. Methods: Using Nanostring technology and comparative bioinformatics, we analysed the expression of 787 fibrosis-related genes in 36 ileal surgical specimens, 12 B2 and 24 B3, the latter including 12 cases with associated stricture[s] [B3s] and 12 without [B3o]. Quality control of extracted RNA was performed according to Nanostring parameters and principal component analysis for the distribution analysis. For the selection of the differentially expressed genes, a p-adjusted Results: We included 34 patients with B2 and B3 phenotypes, balanced for age at diagnosis, age at surgery, gender, Crohn’s disease localisa tion, perianal disease, and therapy. Inflammation and fibrosis histopathological scoring were similar in all cases. B2 and B3 groups showed a very good clustering regarding 30 significantly differentially expressed genes, all being remarkably upregulated in B3. More than half of these genes were involved in Crohn’s disease fibrogenesis, and eight differentially expressed genes were so in other organs. The most significantly active biological processes and pathways in penetrating disease were response to TGFβ and matrix organisation and degradation, as validated by immunohistochemistry. Conclusions: Despite the histopathological similarities in fibrosis between stricturing and penetrating ileal Crohn’s disease, their fibrosis-related transcriptomic profiles are distinct. Penetrating disease exhibits a distinctive transcriptomic landscape related to enhanced matrix remodelling.
- Ileal Crohn's Disease Exhibits Similar Transmural Fibrosis Irrespective of PhenotypePublication . Sousa, Helena Tavares; Gullo, Irene; Castelli, Claudia; Dias, Cláudia Camila; Rieder, Florian; Carneiro, Fátima; Magro, FernandoTransmural inflammation and submucosal fibrosis are important hallmarks of Crohn’s disease (CD) (1). Intestinal fibrosis concerns extracellular matrix accumulation and mesenchymal cell expansion (2,3). In this process, inflammation is the main activator of mesenchymal cells and an essential factor to initiate fibrogenesis. Still, once fibrosis is established, it may be selfpropagating (3,4). In the setting of CD, patients with inflammatory lesions are considered medical therapy-responsive, while those with more fibrotic lesions will eventually need surgery (4). Hence, despite all the available therapies targeting inflammation, intestinal fibrosis remains difficult to treat and pre vent (3,4). Strictures are subdivided in fibrotic, inflammatory, and mixed forms (5). Pure fibrotic or inflammatory strictures are rare, with both components presenting overlapped histopathology (3,6–10). In CD, transmural intestinal inflammation can be assessed by cross-sectional imaging (2,11–16). On the other hand, fibrosis cannot be measured by this technique nor through biomarkers (16,17). Endoscopy or biopsy-based histology (2,11) is not feasible as tissue remodeling occurs mostly in deeper layers (18). Thus, the extent and severity of fibrosis must be evaluated by histopathological analysis of intestinal resection specimens, resorting to several histopathological scoring systems (19,20). The main objective of our work was to characterize and quantify inflammation and fibrosis, in ileal CD resection specimens, according to a CD transmural histopathological scoring system. We also aimed to correlate inflammation and fibrosis profiles with progressive disease.