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Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The intestinal epithelial barrier maintains gut homeostasis, and its disruption contributes to inflammatory diseases such as Inflammatory Bowel Diseases (IBD). Although barrier restoration is a promising therapeutic strategy, most current approaches target immune responses rather than epithelial function. Since barrier injury and repair progress through discrete phases, this study aimed to define time-resolved epithelial transcriptional programs and identify candidate regulatory nodes for barrier-focused therapeutic intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentiated Caco-2 epithelial monolayers were used to model cytokine-induced barrier disruption and profiled by time-resolved bulk RNA-seq. Transcriptional dynamics and candidate regulators were identified using pairwise differential expression, likelihood-ratio testing, pathway enrichment, and upstream-regulator inference. Candidate nodes were tested by pharmacologic perturbation, and disease relevance was assessed by qPCR and histology in human IBD colon tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Time-resolved profiling revealed dynamic epithelial programs involving the Rho GTPase cycle, sirtuin signaling, non-canonical WNT signaling, and junction\/EMT-associated pathways. Upstream-regulator inference highlighted JAK2, TNF, gasdermin D, and \u03b2-estradiol, and pharmacologic perturbation of these nodes mitigated cytokine-induced barrier loss. HNF4A emerged as a gut epithelial transcriptional hub regulating targets including SATB2 and SLC26A3. Notably, SLC26A3 was markedly reduced in IBD colon tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides a time-resolved epithelial framework and highlights therapeutic opportunities for barrier-focused interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-026-02288-5","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T08:08:15Z","timestamp":1780906095000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal transcriptomic profiling identifies core regulators in cytokine-induced gut barrier disruption in differentiated Caco-2 cells"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0869-6156","authenticated-orcid":false,"given":"Hyo Shin","family":"Yoon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shining","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Kanke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Jung","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uyen","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Wilks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sundeep","family":"Chandra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno","family":"Van Lookeren Campagne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0946-9270","authenticated-orcid":false,"given":"Cheng-Yuan","family":"Kao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"2288_CR1","doi-asserted-by":"publisher","unstructured":"Okumura R, Takeda K. 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