Cellular and Molecular Gastroenterology and Hepatology最新文献

{"title":"Stromal Niche Signals That Orchestrate Intestinal Regeneration","authors":"Helen E. Abud ,&nbsp;Shanika L. Amarasinghe ,&nbsp;Diana Micati ,&nbsp;Thierry Jardé","doi":"10.1016/j.jcmgh.2024.02.003","DOIUrl":"10.1016/j.jcmgh.2024.02.003","url":null,"abstract":"<div><p>Stromal cell populations have a central role in providing signals that support the maintenance, differentiation, and function of the intestinal epithelium. The behavior and fate of epithelial cells is directed by the spatial organization of stromal cells that either sustain stem and progenitor cell identity or drive differentiation. A combination of single-cell analyses, mouse models, and organoid coculture assays have provided insight into the diversity of signals delivered by stromal cells. Signaling gradients are established and fine-tuned by the expression of signaling agonists and antagonists along the crypt-villus axis. On epithelial injury, there are disruptions to the abundance and organization of stromal populations. There are also distinct changes in the signals originating from these cells that impact remodeling of the epithelium. How these signals coordinate to mediate epithelial repair or sustain tissue injury in inflammatory bowel diseases is beginning to emerge. Understanding of these processes may lead to opportunities to target stromal cell populations as a strategy to modify disease states.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 5","pages":"Pages 679-685"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000316/pdfft?md5=8c4c0d9049eefe0f57825e81339fb61b&pid=1-s2.0-S2352345X24000316-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Interleukin 33–T Helper 2 Cell Axis Promotes Human Liver Fibrosis","authors":"Isabella Lurje,&nbsp;Frank Tacke","doi":"10.1016/j.jcmgh.2024.01.004","DOIUrl":"10.1016/j.jcmgh.2024.01.004","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 4","pages":"Pages 657-659"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000043/pdfft?md5=68e1b801e29bd6ca126808e22fa66615&pid=1-s2.0-S2352345X24000043-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139587684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial-Fibroblast Crosstalk in Eosinophilic Esophagitis","authors":"Amanda B. Muir ,&nbsp;Tatiana A. Karakasheva ,&nbsp;Kelly A. Whelan","doi":"10.1016/j.jcmgh.2024.01.020","DOIUrl":"10.1016/j.jcmgh.2024.01.020","url":null,"abstract":"<div><p>Eosinophilic esophagitis (EoE) is an emerging form of food allergy that exerts a significant clinical and financial burden worldwide. EoE is clinically characterized by eosinophil-rich inflammatory infiltrates in esophageal mucosa and esophageal dysfunction. Remodeling events in esophageal epithelium and lamina propria also frequently occur in patients with EoE. Because subepithelial fibrosis is associated with esophageal stricture, the most severe consequence of EoE, there exists an urgent need for a deeper understanding of the molecular mechanisms mediating fibrosis in EoE. Here, we review emerging evidence from experimental model systems that implicates crosstalk between esophageal epithelial cells and underlying stromal cells in EoE fibrosis. We further discuss implications for epithelial-stromal interaction with regard to EoE patient care and propose future directions that may be pursued to further the understanding of epithelial-stromal crosstalk in EoE pathobiology.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 5","pages":"Pages 713-718"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000237/pdfft?md5=d1bf96f096f826b703b4ba9002f49572&pid=1-s2.0-S2352345X24000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the Roles of Cancer-Associated Fibroblasts in Pancreatic Cancer","authors":"Ralph Francescone ,&nbsp;Howard C. Crawford ,&nbsp;Debora Barbosa Vendramini-Costa","doi":"10.1016/j.jcmgh.2024.01.022","DOIUrl":"10.1016/j.jcmgh.2024.01.022","url":null,"abstract":"<div><p>Bearing a dismal 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is a challenging disease that features a unique fibroinflammatory tumor microenvironment. As major components of the PDAC tumor microenvironment, cancer-associated fibroblasts are still poorly understood and their contribution to the several hallmarks of PDAC, such as resistance to therapies, immunosuppression, and high incidence of metastasis, is likely underestimated. There have been encouraging advances in the understanding of these fascinating cells, but many controversies remain, leaving the field still actively exploring the full scope of their contributions in PDAC progression. Here we pose several important considerations regarding PDAC cancer-associated fibroblast functions. We posit that transcriptomic analyses be interpreted with caution, when aiming to uncover the functional contributions of these cells. Moreover, we propose that normalizing these functions, rather than eliminating them, will provide the opportunity to enhance therapeutic response. Finally, we propose that cancer-associated fibroblasts should not be studied in isolation, but in conjunction with its extracellular matrix, because their respective functions are coordinated and concordant.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 5","pages":"Pages 737-743"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000250/pdfft?md5=f1bd4e8db1394296f5770ca91b13316f&pid=1-s2.0-S2352345X24000250-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT1 Stabilizes β-TrCP1 to Inhibit Snail1 Expression in Maintaining Intestinal Epithelial Integrity to Alleviate Colitis","authors":"Liang Wang ,&nbsp;Jinsong Li ,&nbsp;Mingshan Jiang ,&nbsp;Yue Luo ,&nbsp;Xiaoke Xu ,&nbsp;Juan Li ,&nbsp;Yang Pan ,&nbsp;Hu Zhang ,&nbsp;Zhi-Xiong Jim Xiao ,&nbsp;Yang Wang","doi":"10.1016/j.jcmgh.2024.05.002","DOIUrl":"10.1016/j.jcmgh.2024.05.002","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to inflammatory bowel disease (IBD). The NAD⁺-dependent deacetylase SIRT1 is implicated in inflammation and the pathologic process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity.</p></div><div><h3>Methods</h3><p>The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and wild-type mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes was analyzed. Intestinal permeability was measured by FITC-dextran and cytokines expression was analyzed by quantitative polymerase chain reaction. The expression of the cell junction–related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of nicotinamide mononucleotide in DSS-induced mice colitis were investigated. Correlations of the SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed.</p></div><div><h3>Results</h3><p>Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. The activation of SIRT1 by nicotinamide mononucleotide bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS downregulates SiRT1 expression, leading to destabilization of β-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-β-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD.</p></div><div><h3>Conclusions</h3><p>SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the β-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 2","pages":"Article 101354"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24001085/pdfft?md5=ec34af7822631db47d221e53a4b22e02&pid=1-s2.0-S2352345X24001085-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replication Efficiency of SARS-CoV-2 Omicron Subvariants BA.2.75, BA.5, and XBB.1 in Human Mini-Gut Organoids","authors":"Kei Miyakawa,&nbsp;Masakazu Machida,&nbsp;Tomoyuki Kawasaki,&nbsp;Masatoshi Kakizaki,&nbsp;Yayoi Kimura,&nbsp;Masaya Sugiyama,&nbsp;Hideki Hasegawa,&nbsp;Akihiro Umezawa,&nbsp;Hidenori Akutsu,&nbsp;Akihide Ryo","doi":"10.1016/j.jcmgh.2024.03.003","DOIUrl":"10.1016/j.jcmgh.2024.03.003","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 6","pages":"Pages 1066-1068"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000559/pdfft?md5=11f8ae8dd4372508c084a3a512815b8d&pid=1-s2.0-S2352345X24000559-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatocellular RECK as a Critical Regulator of Metabolic Dysfunction-associated Steatohepatitis Development","authors":"Ryan J. Dashek ,&nbsp;Rory P. Cunningham ,&nbsp;Christopher L. Taylor ,&nbsp;Isabella Alessi ,&nbsp;Connor Diaz ,&nbsp;Grace M. Meers ,&nbsp;Andrew A. Wheeler ,&nbsp;Jamal A. Ibdah ,&nbsp;Elizabeth J. Parks ,&nbsp;Tadashi Yoshida ,&nbsp;Bysani Chandrasekar ,&nbsp;R. Scott Rector","doi":"10.1016/j.jcmgh.2024.101365","DOIUrl":"10.1016/j.jcmgh.2024.101365","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is an extracellular matrix regulator with anti-fibrotic effects. However, its expression and role in metabolic dysfunction-associated steatohepatitis (MASH) and hepatic fibrosis are poorly understood.</p></div><div><h3>Methods</h3><p>We generated a novel transgenic mouse model with RECK overexpression specifically in hepatocytes to investigate its role in Western diet (WD)-induced liver disease. Proteomic analysis and in vitro studies were performed to mechanistically link RECK to hepatic inflammation and fibrosis.</p></div><div><h3>Results</h3><p>Our results show that RECK expression is significantly decreased in liver biopsies from human patients diagnosed with MASH and correlated negatively with severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis. Similarly, RECK expression is downregulated in WD-induced MASH in wild-type mice. Hepatocyte-specific RECK overexpression significantly reduced hepatic pathology in WD-induced liver injury. Proteomic analysis highlighted changes in extracellular matrix and cell-signaling proteins. <em>In vitro</em> mechanistic studies linked RECK induction to reduced ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) and ADAM17 activity, amphiregulin release, epidermal growth factor receptor activation, and stellate cell activation.</p></div><div><h3>Conclusion</h3><p>Our in vivo and mechanistic in vitro studies reveal that RECK is a novel upstream regulator of inflammation and fibrosis in the diseased liver, its induction is hepatoprotective, and thus highlights its potential as a novel therapeutic in MASH.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 3","pages":"Article 101365"},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X2400119X/pdfft?md5=9bce892f2c6acfc5041f78bf7188f749&pid=1-s2.0-S2352345X2400119X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141137953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbial-Dependent Recruitment of Immature Myeloid Cells Promotes Intestinal Regeneration","authors":"Zhengyu Jiang ,&nbsp;Quin T. Waterbury ,&nbsp;Ermanno Malagola ,&nbsp;Na Fu ,&nbsp;Woosook Kim ,&nbsp;Yosuke Ochiai ,&nbsp;Feijing Wu ,&nbsp;Chandan Guha ,&nbsp;Carrie J. Shawber ,&nbsp;Kelley S. Yan ,&nbsp;Timothy C. Wang","doi":"10.1016/j.jcmgh.2023.10.007","DOIUrl":"10.1016/j.jcmgh.2023.10.007","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>The intestinal epithelium functions both in nutrient absorption and as a barrier, separating the luminal contents from a network of vascular, fibroblastic, and immune cells underneath. After injury to the intestine, multiple cell populations cooperate to drive regeneration of the mucosal barrier, including lymphatic endothelial cells (LECs). A population of granulocytic immature myeloid cells (IMCs), marked by <em>Hdc</em>, participate in regeneration of multiple organs such as the colon and central nervous system, and their contribution to intestinal regeneration was investigated.</p></div><div><h3>Methods</h3><p>By using male and female histidine decarboxylase (Hdc) green fluorescent reporter (GFP) mice, we investigated the role of Hdc⁺ IMCs in intestinal regeneration after exposure to 12 Gy whole-body irradiation. The movement of IMCs was analyzed using flow cytometry and immunostaining. Ablation of Hdc⁺ cells using the Hdc^CreERT2 tamoxifen-inducible recombinase Cre system, conditional knockout of Prostaglandin-endoperoxidase synthase 2 (<em>Ptgs2</em><em>)</em> in Hdc⁺ cells using Hdc^Cre; Ptgs2 floxed mice, and visualization of LECs using Prox1^tdTomato mice also was performed. The role of microbial signals was investigated by knocking down mice gut microbiomes using antibiotic cocktail gavages.</p></div><div><h3>Results</h3><p>We found that Hdc⁺ IMCs infiltrate the injured intestine after irradiation injury and promote epithelial regeneration in part by modulating LEC activity. Hdc⁺ IMCs express <em>Ptgs2</em> (encoding cyclooxygenase-2/COX-2), and enables them to produce prostaglandin E₂. Prostaglandin E₂ acts on the prostaglandin E₂ receptor 4 receptor (EP4) on LECs to promote lymphangiogenesis and induce the expression of proregenerative factors including R-spondin 3. Depletion of gut microbes leads to reduced intestinal regeneration by impaired recruitment of IMCs.</p></div><div><h3>Conclusions</h3><p>Altogether, our results unveil a critical role for IMCs in intestinal repair by modulating LEC activity and implicate gut microbes as mediators of intestinal regeneration.</p></div>","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"17 3","pages":"Pages 321-346"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X23001868/pdfft?md5=cd8dff9258af4c6988d6e5fbf33d2526&pid=1-s2.0-S2352345X23001868-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66784645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteroendocrine Cell Loss Drives Small Intestinal Hypomotility in Colitis","authors":"Jacques Gonzales","doi":"10.1016/j.jcmgh.2024.03.012","DOIUrl":"10.1016/j.jcmgh.2024.03.012","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 1","pages":"Pages 157-158"},"PeriodicalIF":7.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000675/pdfft?md5=209f8a374b09eda8431f8715551e4b13&pid=1-s2.0-S2352345X24000675-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140767454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking Down the Pain Pathway: Bacterial Proteases Activate Nociceptors to Cause Pain","authors":"","doi":"10.1016/j.jcmgh.2024.03.009","DOIUrl":"10.1016/j.jcmgh.2024.03.009","url":null,"abstract":"","PeriodicalId":55974,"journal":{"name":"Cellular and Molecular Gastroenterology and Hepatology","volume":"18 4","pages":"Article 101337"},"PeriodicalIF":7.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352345X24000614/pdfft?md5=648684eeec273507741a68d0e08c1416&pid=1-s2.0-S2352345X24000614-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140782726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}