{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T09:13:36Z","timestamp":1788858816724,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANPCYT","award":["PICT-2021-CATI00066"],"award-info":[{"award-number":["PICT-2021-CATI00066"]}]},{"DOI":"10.13039\/501100003947","name":"University of La Plata, Argentina","doi-asserted-by":"publisher","award":["X989"],"award-info":[{"award-number":["X989"]}],"id":[{"id":"10.13039\/501100003947","id-type":"DOI","asserted-by":"publisher"}]},{"award":["X989"],"award-info":[{"award-number":["X989"]}],"id":[{"id":"https:\/\/ror.org\/01tjs6929","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Fiorini 2025"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Juvenile colorectal polyps (JP) are the most common polypoid lesions of the colon in children and the leading cause of lower gastrointestinal bleeding in pediatric patients. Although histologically classified as benign hamartomatous lesions, they arise in a context of allergic sensitization and IgE-mediated inflammation, suggesting that the epithelial compartment may play an active role in their pathogenesis. To date, most studies have focused on the immune cell infiltrate, leaving the molecular programs operating within the epithelium largely unexplored. Whole-transcriptome RNA sequencing (RNA-seq) was performed on epithelial cells isolated from pediatric JP (n = 8) and paired tissue circumjacent to polyp (TCP) (n = 7) obtained from children with a history of rectal bleeding and IgE sensitization to food allergens. Differential expression, functional enrichment (GO, KEGG, GSEA), and cross-dataset comparison with TCGA colorectal adenocarcinoma (CRC) was conducted. Candidate genes were validated by RT-qPCR in independent samples, including colorectal cancer (CRC) and inflammatory bowel disease (IBD) tissue. Differential expression analysis identified 3273 differentially expressed genes (2342 upregulated, 931 downregulated in JP vs. TCP), with 220 genes exceeding 32-fold change, including SERPINB3 (log2FC = 12.16), MMP1 (log2FC = 10.19), NMUR2 (log2FC = 10.08) and CHI3L1 (log2FC = 8.87). JP epithelium displayed a coherent type 2 inflammatory signature, encompassing upregulation of the alarmin IL33, eosinophil-attracting chemokines (CCL11, CCL24), IgE receptor subunits (FCER1A, FCER1G), and a coordinately activated leukotriene and prostaglandin biosynthetic program (ALOX5, ALOX5AP, PTGS2). Concurrent alterations in epithelial identity were observed, including downregulation of absorptive enterocyte and intestinal stem cell markers (CDX2, LGR5, ASCL2) alongside upregulation of secretory and regenerative programs, including the ectopic gastric-type mucin MUC5AC. Tight junction dysregulation\u2014notably upregulation of the pore-forming claudin CLDN2 and loss of barrier-sealing claudins (CLDN3, CLDN4, CLDN23)\u2014was consistent with impaired epithelial permeability. Pathway analyses confirmed activation of type 2 immune and extracellular matrix remodeling programs, with concurrent suppression of mitochondrial oxidative phosphorylation. Cross-dataset comparison with TCGA CRC data identified 381 co-upregulated and 87 co-downregulated genes shared between JP and CRC, including SERPINE1, CXCL8, ICAM1, and MMP3, several of which were associated with poorer disease-specific survival in CRC patients. RT-qPCR validation confirmed elevation of CHI3L1 and SERPINE1 in both JP and CRC, while SERPINB4 appeared JP-specific. Epithelial cells from pediatric juvenile colorectal polyps associated with allergic sensitization display a comprehensive type 2 inflammatory transcriptome alongside profound alterations in lineage identity, barrier integrity, and metabolic programming. Partial convergence with CRC-associated gene expression programs\u2014in the absence of histological dysplasia\u2014suggests that chronic allergic inflammation activates conserved epithelial remodeling pathways shared across mucosal tissues. CHI3L1, SERPINE1, and SERPINB4 are candidate biomarkers warranting validation in larger cohorts.<\/jats:p>","DOI":"10.3390\/ijms27177946","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"7946","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Conserved Epithelial Remodeling Programs Underlie Pediatric Juvenile Colorectal Polyps Associated with Allergic Sensitization"],"prefix":"10.3390","volume":"27","author":[{"given":"Mar\u00eda Bel\u00e9n","family":"Polo","sequence":"first","affiliation":[{"name":"Instituto de Estudios Inmunol\u00f3gicos y Fisiopatol\u00f3gicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Ilid","sequence":"additional","affiliation":[{"name":"Instituto de Estudios Inmunol\u00f3gicos y Fisiopatol\u00f3gicos-IIFP, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Viviana","family":"Bernedo","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Paula","family":"Borobia","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Lorena","family":"Menendez","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1147-9244","authenticated-orcid":false,"given":"Anabella","family":"Zosi","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Cecilia","family":"Zubir\u00ed","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Maximiliano","family":"Fern\u00e1ndez Rivas","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9858-7558","authenticated-orcid":false,"given":"Mar\u00eda Florencia","family":"Recalde","sequence":"additional","affiliation":[{"name":"Servicio de Gastroenterolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Barbara Virginia","family":"Aguilar Becher","sequence":"additional","affiliation":[{"name":"Sala de Alergia, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1983-0285","authenticated-orcid":false,"given":"Marcela","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Sala de Alergia, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda Ludovica, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Eugenia","family":"Altamirano","sequence":"additional","affiliation":[{"name":"Servicio de Patolog\u00eda, Hospital Interzonal de Agudos Especializado en Pediatr\u00eda Sor Mar\u00eda 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