American journal of physiology. Gastrointestinal and liver physiology最新文献

{"title":"Site-specific bidirectional regulation of <i>Fgf15</i> transcription in the mouse ileum.","authors":"Takeshi Katafuchi, Akira Honda, Makoto Makishima","doi":"10.1152/ajpgi.00026.2026","DOIUrl":"10.1152/ajpgi.00026.2026","url":null,"abstract":"<p><p>Fibroblast growth factor 15 (FGF15) plays a crucial role in the negative feedback loop of bile acid (BA) production by reducing mRNA levels of hepatic <i>Cyp7a1</i>, a rate-limiting enzyme of BA synthesis. Here, we investigated the postprandial regulation of <i>Fgf15</i> mRNA levels in the ileum to unveil the physiological regulation of FGF15 production by feeding in mice. The postprandial <i>Fgf15</i> mRNA level reached the minimum level in the distal ileum following starvation for 20 h and subsequent feeding for 3 h. In mice lacking tauro-β-muricholic acid, which is an endogenous antagonist for the farnesoid-X-receptor (FXR), the <i>Fgf15</i> mRNA level in the distal ileum was still 3 h-postprandially reduced. We further explored the postprandial regulation of <i>Fgf15</i> transcription in various sites of the ileum and found that the 3 h-postprandial <i>Fgf15</i> levels were reduced in the distal ileum while elevated in the proximal ileum. Furthermore, the 3 h-postprandial plasma FGF15 level was reduced despite the elevated <i>Fgf15</i> mRNA level in the proximal ileum. In mice lacking <i>Fxr</i> in the intestine, the relative amount of 3 h-postprandial <i>Fgf15</i> mRNA level was still reduced in the distal ileum, whereas the 3 h-postprandial elevation was blunt in the proximal ileum. Oral administration of soybean oil, fatty acids, and PPARγ agonist pioglitazone reduced <i>Fgf15</i> expression in the distal ileum, indicating that PPARγ signaling is involved in the negative regulation of <i>Fgf15</i> mRNA level. Collectively, our data show the complicated regulation of plasma FGF15 concentration by bidirectional change in <i>Fgf15</i> mRNA levels by food intake in different sites of the ileum.<b>NEW & NOTEWORTHY</b> It is considered that feeding stimulates the release of bile acids, which ultimately bind to FXR to increase the <i>Fgf15</i> transcription in the ileum. However, we found that <i>Fgf15</i> mRNA levels were postprandially reduced, particularly in the distal ileum, and this reduction was mediated through fatty acid-PPARγ signaling. In the proximal ileum, however, we observed that <i>Fgf15</i> mRNA levels were postprandially elevated through bile acid-FXR signaling, which was consistent with the current idea.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G601-G614"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring autonomic influence on gastrointestinal contractility: development and preliminary validation of novel capsule-based indices.","authors":"Mitali Mehta, Zhan Zhao, Asala Erekat, Jack Semler, Niyati Neupane, Bridget R Mueller, Kaitlyn Coyle, Gabriela Cedillo, Jessica Robinson-Papp","doi":"10.1152/ajpgi.00006.2026","DOIUrl":"10.1152/ajpgi.00006.2026","url":null,"abstract":"<p><p>The migrating motor complex (MMC) is a key feature of fasting gastrointestinal (GI) motility, but its disruption in neuropathic conditions remains poorly characterized. Wireless motility capsules (WMCs) offer a noninvasive means of collecting motility data, facilitating study of larger cohorts. We aimed to develop WMC-derived metrics to identify neuropathic dysmotility and its associations with autonomic nervous system (ANS) function. We analyzed WMC data from 98 controls and 71 people living with human immunodeficiency virus (HIV; PWH) in whom autonomic neuropathy (AN) and delayed small bowel transit time (dSBTT) are common. We studied nine contractility metrics, including established and novel metrics targeting rhythmic bursts of sustained contractile activity. Autonomic function, summarized as Modified Composite Autonomic Severity Score (MCASS), was used to draw associations with contractility measures. All contractility metrics were higher in PWH compared with controls (<i>P</i> ≤ 0.01 for all). Among PWH, those with AN showed the highest contractility, whereas those with dSBTT had the lowest. In controls, rhythmic bursts were more clustered, especially in the later portions of the small bowel recording, and had less variability in contraction amplitude and timing, potentially indicating greater organization. Overall, worse autonomic function was associated with higher contractility. WMC-derived metrics effectively capture fasting small bowel motility and may distinguish neuropathic patterns, which appear to progress from increased, disorganized contractility to decreased contractility as dSBTT develops. Future studies should validate these findings in other WMCs and populations to clarify their potential in advancing understanding of the pathophysiology of gut-brain-axis disorders.<b>NEW & NOTEWORTHY</b> This study introduces novel WMC-derived contractility indices to quantify gastrointestinal motility, enabling noninvasive characterization of neuropathic dysmotility. In PWH, hypercontractility and disorganized rhythmic bursts were observed despite autonomic neuropathy and delayed transit, suggesting a spectrum in which inefficient high-amplitude contractions initially may preserve transit before progressive delay ensues. Leveraging raw pressure data from WMC technology, these indices are linkable to extrinsic autonomic biomarkers and may advance understanding of gut-brain axis disorder pathophysiology.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G633-G644"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF-α alters dedifferentiation of enterochromaffin cells, redirecting toward neuroendocrine tumors.","authors":"Yoshitatsu Sei, Jianying Feng, Xilin Zhao, Stephen A Wank","doi":"10.1152/ajpgi.00407.2025","DOIUrl":"10.1152/ajpgi.00407.2025","url":null,"abstract":"<p><p>Small intestinal neuroendocrine tumors (SI-NETs) are serotonin-secreting, well-differentiated neuroendocrine tumors of enterochromaffin (EC) cell origin. However, EC cell-derived tumorigenesis remains poorly understood. Prior studies using TPH1 Cre-ERT2-driven RPM mice [EC cell-targeted RB1 (R) and Trp53 (P) loss and Myc (M) gain] showed nonendocrine adenocarcinomas in the small intestine through dedifferentiation of EC cells to intestinal stem cells, which are prone to transformation. However, these studies were limited by early death from tumors at other sites, leaving the potential for SI-NET development unclear over longer periods. To circumvent this time-limited off-target effect, the present study used intestinal enteroids from RPM mice to examine the effect of RB1 and Trp53 loss with or without gain of Myc function on EC cell-derived tumors. Initial results confirmed the previous in vivo induction of nonendocrine adenoma/adenocarcinoma. However, the addition of TNF-α to the enteroid media induced EC cell clusters in multiple crypts and well-differentiated neuroendocrine tumor versus carcinoma in the absence and presence of gain of Myc function, respectively. These findings suggest that TNF-α blocked EC cell dedifferentiation to intestinal stem cells, promoting their survival and expansion and shifting their fate from intestinal adenoma/carcinoma to a differentiated neuroendocrine tumor type. The present study thus highlights the crucial role of the microenvironment in influencing EC cell-derived tumorigenesis and provides insights into SI-NET development.<b>NEW & NOTEWORTHY</b> Small intestinal neuroendocrine tumors are of putative enterochromaffin (EC) cell origin and are the most common malignancy in the small intestine. However, the tumorigenesis of these specified tumor types remains poorly understood. The present organoid studies show that the addition of TNF-α to the microenvironment maintains the specificity of EC cells during their transformation to neuroendocrine tumors while blocking their dedifferentiation to ISC-derived adenomas.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G581-G590"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting VTCN1 overcomes immunosuppression in colorectal cancer to activate T cells via galectin-3.","authors":"Zhihai Wu, Jiayi Zhong, Chengcheng Xu, Chengkuan Zhao, Qin Yang, Lili Zhao, Chaoxian Lin, Shuyao Zhang, Junyong Zhong","doi":"10.1152/ajpgi.00323.2025","DOIUrl":"10.1152/ajpgi.00323.2025","url":null,"abstract":"<p><p>Colorectal cancer (CRC) continues to be a major cause of cancer-related death globally, largely due to mechanisms of immune evasion that drive treatment resistance. Although multidisciplinary care has improved outcomes, how immune checkpoint molecules, particularly V-set domain-containing T-cell activation inhibitor 1 (VTCN1) and galectin-3, drive immunosuppression in CRC remains incompletely defined. In this study, we used an integrated multi-omics framework combining single-cell sequencing, transcriptomics, and proteomics to delineate the VTCN1-galectin-3 axis in CRC. We then validated its functional relevance using the VTCN1 inhibitor SGN-B7H4 in vitro and in vivo by assessing T cell function and tumor progression. Our results show that inhibiting VTCN1 markedly downregulates galectin-3 expression in T cells (<i>P</i> < 0.01), promoting T cell activation, as reflected by a 42% increase in CD25+CD69+ populations. Consequently, CRC cell proliferation was reduced by 58%, migration by 72% in scratch assays, and invasion by 65% in Transwell assays. In mouse models, SGN-B7H4 administration suppressed tumor growth by 63% relative to controls. These outcomes identify the VTCN1-galectin-3 axis as a pivotal mediator of immune suppression in CRC and highlight the therapeutic promise of targeting this pathway. Our work underscores the potential of VTCN1 inhibitors as part of combined treatment modalities, especially for immunotherapy-resistant CRC.<b>NEW & NOTEWORTHY</b> This study identifies the V-set domain-containing T-cell activation inhibitor 1 (VTCN1)-galectin-3 axis as a key immunosuppressive pathway in colorectal cancer (CRC). We show that inhibiting VTCN1 downregulates galectin-3 in T cells, reversing their dysfunction and reactivating antitumor immunity. Therapeutically, the VTCN1 inhibitor SGN-B7H4 restricted tumor progression by enhancing T-cell activity and impairing cancer cell proliferation, migration, and invasion. These findings reveal a novel immune checkpoint mechanism and establish VTCN1 as a promising target to overcome immunotherapy resistance in CRC.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G615-G632"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis.","authors":"Xiaoying S Zhong, Kevin M Lopez, Max Liu, Ying Xiao, Rongliwen Ou, Thierry Kochkarian, Don W Powell, Ken Fujise, Qingjie Li","doi":"10.1152/ajpgi.00324.2025","DOIUrl":"10.1152/ajpgi.00324.2025","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestines accompanied by profound extraintestinal manifestations. Although IBD shows a clear clinical association with cardiovascular derangements, whether and how chronic colitis impairs heart function remains unclear. To address this gap, we investigated the impact of chronic colitis on cardiac performance and the cardiac transcriptome using two mouse models: dextran sodium sulfate (DSS)-treated and <i>Il10^-/-</i> mice. Heart function was assessed by echocardiography and molecular characterization was performed using RNA-sequencing (RNA-Seq), reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and Western blot. Both models exhibited significant functional cardiac impairment, characterized by reduced ejection fraction and fractional shortening along with histologically evident increase in collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed a profibrotic cardiac environment. RNA sequencing unveiled a shared upregulation of eicosanoid-associated and inflammatory genes (<i>Cyp2e1</i>, <i>Map3k6</i>, <i>Pck1</i>, and <i>Cfd</i>) across both models, alongside model-specific alterations in pathways governing cAMP and cGMP signaling, arachidonic and linoleic acid metabolism, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, whereas <i>Il10^-/-</i> colitis yielded 105 dysregulated genes. Notably, reconstitution of a healthy balance of gut microbiota by therapeutic fecal microbiota transplantation (FMT), validated using quantitative polymerase chain reaction (qPCR), successfully rescued heart function and mitigated fibrosis in both models. However, <i>Il10^-/-</i> mice demonstrated relatively less cardiac recovery following FMT, highlighting interleukin-10 (IL-10)'s cardioprotective and anti-inflammatory contribution. Collectively, these findings provide evidence that chronic colitis impairs heart function, offer novel insights into colitis-induced cardiac remodeling, and suggest that FMT mitigates cardiac dysfunction by correcting gut dysbiosis, attenuating systemic inflammation, and reestablishing homeostasis along the gut-heart axis.<b>NEW & NOTEWORTHY</b> Inflammatory bowel disease (IBD) extends beyond the gut, as chronic inflammation and microbiota dysbiosis contribute to serious extraintestinal complications. This study demonstrates that chronic colitis induces cardiac remodeling and dysfunction in two mouse models, marked by reduced cardiac performance, fibrosis, and upregulated fibrotic and inflammatory genes. Importantly, fecal microbiota transplantation (FMT) alleviated cardiac injury, highlighting its therapeutic potential. These findings reveal FMT as a promising therapy against chronic inflammation contributing to cardiovascular complications in IBD.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G565-G580"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher's note.","authors":"","doi":"10.1152/ajpgi.00107.2026_NOT","DOIUrl":"https://doi.org/10.1152/ajpgi.00107.2026_NOT","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"330 5","pages":"G657"},"PeriodicalIF":3.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brown adipose tissue inactivation exacerbates alcohol-induced liver steatosis, inflammation, and fibrosis.","authors":"Qing Zhang, Zhiguo Zhang, Liangyou Rui","doi":"10.1152/ajpgi.00336.2025","DOIUrl":"10.1152/ajpgi.00336.2025","url":null,"abstract":"<p><p>Alcohol-induced liver fibrosis is a devastating manifestation of alcohol-related liver disease (ALD). However, conventional mouse models fail to recapitulate this fibrotic phenotype, limiting their translational relevance. Mice develop and retain robust brown adipose tissue (BAT) for thermoregulation, which confers protection against hepatic steatosis. Here, we identify BAT as a key protective tissue against alcohol-induced liver fibrosis in mice. BAT was inactivated in mice via denervation or surgically ablated, followed by 8 wk of chronic plus binge alcohol exposure. Both BAT denervation and ablation markedly exacerbated hepatic steatosis, injury, and inflammation compared with sham controls. Remarkably, BAT inactivation or ablation induced robust hepatic stellate cell (HSC) activation and liver fibrosis in both sexes, as evidenced by increased α-smooth muscle actin expression, enhanced Sirius red and Masson's trichrome staining, and elevated hydroxyproline content. These fibrotic changes were absent in sham-operated controls. Mechanistically, BAT-conditioned medium-containing BAT-secreted batokines-induced lipid accumulation, oxidative stress, and cell injury in hepatocyte cultures. Furthermore, batokines directly targeted cultured macrophages and HSCs and suppressed their activities. Collectively, these results unveil a hepatoprotective role of BAT and batokines in ALD progression and establish a physiologically and translationally relevant mouse model of ALD by combining BAT inactivation with chronic plus binge alcohol exposure.<b>NEW & NOTEWORTHY</b> Brown adipose tissue confers resistance to alcohol-related liver disease through secreting batokines. Inactivation of brown fat exacerbates alcohol-induced liver steatosis, inflammation, and fibrosis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G381-G396"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pilot, randomized, placebo-controlled trial of rimegepant on visceral sensation and symptoms in nonconstipation IBS pain.","authors":"Houssam Halawi, Ayah Matar, Iris Wang, Kara J Jencks, Irene Busciglio, Deborah Eckert, William S Harmsen, Michael Camilleri","doi":"10.1152/ajpgi.00394.2025","DOIUrl":"10.1152/ajpgi.00394.2025","url":null,"abstract":"<p><p>Visceral hypersensitivity is a pivotal mechanism in pain associated with irritable bowel syndrome (IBS). Calcitonin gene-related peptide (CGRP) is expressed by visceral afferents. The aim of this study was to evaluate the efficacy of rimegepant, a CGRP antagonist, on abdominal pain, rectal compliance and sensation, gut transit, and safety in participants with nonconstipation IBS with pain. We conducted a pilot, randomized, double-blind, placebo-controlled, parallel-group design trial (NCT06221111) of oral rimegepant 75 mg every other day (as approved for migraine prophylaxis) in adults with nonconstipation IBS pain. The trial consisted of three periods: 2-wk run-in, 4-wk treatment, and 4-wk post-treatment with diary recording of daily abdominal pain (primary endpoint) and bowel movements (BMs). Rectal compliance and sensation were measured using barostat distensions and gastrointestinal and colonic transit by scintigraphy. Statistical analysis compared rimegepant with placebo using analysis of covariance with sex, level of anxiety, and baseline measurements as covariates. Twenty-four participants were randomized to rimegepant (<i>n</i> = 12) or placebo (<i>n</i> = 12); baseline demographics, rectal sensation, and compliance were similar between the groups. Rimegepant did not significantly reduce abdominal pain, daily BM frequency, or BM consistency relative to baseline. Compared with placebo, rimegepant significantly reduced sensations of gas, urgency, and pain during 24 mmHg, and gas and urgency sensations during 36 mmHg rectal distension (all <i>P</i> ≤ 0.05 unadjusted). Rimegepant decreased rectal compliance. No significant effects were noted during washout. There were no serious adverse events or adverse events of ≥ Grade 3 severity. Rimegepant's effects on rectal sensation suggest further studies in nonconstipation IBS pain are warranted. Clinical Trial Registry Number: NCT06221111.<b>NEW & NOTEWORTHY</b> This pilot, randomized, double-blind trial in a relatively small sample of patients with IBS-related pain shows rimegepant significantly reduced sensations of gas, urgency, and pain during rectal distention and decreased rectal compliance. Decrease in compliance implies that changes in physical properties or distensibility of rectum did not contribute to alterations in rectal sensation. Same dose of rimegepant did not significantly impact daily abdominal pain, BM frequency, or colonic transit. There were no serious adverse events.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G369-G380"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGK1 signaling: an important modulator of CFTR function and early immune response in mouse intestine.","authors":"Caroline Muiler, Anderson Santos, Nadia A Ameen","doi":"10.1152/ajpgi.00400.2025","DOIUrl":"10.1152/ajpgi.00400.2025","url":null,"abstract":"<p><p>Glucocorticoid (GC) and stress-induced serum- and glucocorticoid-inducible kinase 1 (SGK1) signaling rapidly modulate intestinal epithelial transport, yet whether epithelial SGK1 is required to couple GC signaling to functional cystic fibrosis transmembrane conductance regulator (CFTR) output in vivo has remained unclear. We examined this question using <i>Villin-Cre;Sgk1</i>^flox/flox conditional knockout (<i>Sgk1</i>cKO) and littermate heterozygous controls (<i>Sgk1</i>cHET) mice treated with dexamethasone (DEX; 2 mg/kg ip) for 1 or 4 h. Outcomes included CFTR protein abundance, immunolocalization (immunoblotting and immunofluorescence), CFTR-ion transport measured by short-circuit current (<i>I</i>_sc) in Ussing chambers, epithelial <i>Sgk1/2/3</i> expression, intestinal loop fluid accumulation, and CD45⁺ cell signal as a readout of early immune engagement. Acute DEX treatment activated SGK1 signaling and elevated CFTR protein in <i>Sgk1</i>cHET but also in <i>Sgk1</i>cKO. However, only <i>Sgk1</i>cHET exhibited a rise in CFTR-dependent Δ<i>I</i>_sc, whereas <i>Sgk1</i>cKO failed to increase secretion despite higher total CFTR. <i>Sgk2</i> and <i>3</i> were upregulated in <i>Sgk1</i>cKO but did not restore function. CD45⁺ signal rose transiently at 1 h and normalized by 4 h, consistent with early, self-limited immune engagement. In an intestinal loop assay, short-term DEX treatment did not exacerbate cGMP-evoked fluid accumulation. Together, these data identify epithelial SGK1 signaling as a necessary node that translates acute stress-induced CFTR stabilization into functional secretion and a transient epithelial-immune response. These findings help reconcile expression-function discrepancies and suggest that targeting SGK1 or its downstream steps may be required to achieve functional CFTR gains under acute stress in the intestine.<b>NEW & NOTEWORTHY</b> Glucocorticoids rapidly boost intestinal CFTR expression, function, and trafficking through SGK1 and link stress signaling to epithelial secretion and immune control. Deleting <i>Sgk1</i> blocked glucocorticoid-driven CFTR activation and altered early immune cell recruitment, uncovering SGK1 as a critical regulator of intestinal adaptation to acute stress.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G487-G494"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction for Berndt et al., volume 303, 2011, p. G1384-G1392.","authors":"","doi":"10.1152/ajpgi.00095.2026_COR","DOIUrl":"https://doi.org/10.1152/ajpgi.00095.2026_COR","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":"330 4","pages":"G495-G497"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}