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

{"title":"Extracellular recordings from the stomach faithfully record slow-wave activity detected using intracellular microelectrodes.","authors":"Tim Hibberd, Nick J Spencer","doi":"10.1152/ajpgi.00217.2024","DOIUrl":"10.1152/ajpgi.00217.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G483-G484"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970441","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":"A novel mouse model of hepatocyte-specific apoptosis-induced myeloid cell-dominant sterile liver injury and repair response.","authors":"Heng-Fu Bu, Saravanan Subramanian, Pauline M Chou, Fangyi Liu, Leyu Sun, Hua Geng, Xiao Wang, Jie Liao, Chao Du, Joyce Hu, Stephanie C Tan, Nirmal Nathan, Guang-Yu Yang, Xiao-Di Tan","doi":"10.1152/ajpgi.00005.2024","DOIUrl":"10.1152/ajpgi.00005.2024","url":null,"abstract":"<p><p>Apoptosis, inflammation, and wound healing are critical pathophysiological events associated with various liver diseases. Currently, there is a lack of in vivo approaches to study hepatocyte apoptosis-induced liver injury and repair. To address this critical knowledge gap, we developed a unique genetically modified mouse model, namely, 3-Transgene (Tg) with inducible Hepatocyte-Specific Apoptosis Phenotype (3xTg-iHAP) in this study. The 3xTg-iHAP mice possess three transgenes including <i>Alb-Cre</i>, Rosa26-<i>rtTA</i>, and <i>tetO-Fasl</i> on a B6 background. These mice are phenotypically normal, viable, and fertile. After subcutaneous administration of a single dose of doxycycline (5 mg/kg, Dox) to 3xTg-iHAP mice, we observed a complete histological spectrum of sterile liver wound-healing responses: asymptomatic hepatocyte apoptosis at 8 h, necrotic liver injury and sterile inflammation at 48 h, followed by hepatocyte mitosis and regeneration within 7 days. During the injury phase, the mice exhibited an increase in the biomarkers of alanine aminotransferase (ALT), chemokine (C-X-C motif) ligand 1 (CXCL1), and IL-6 in peripheral blood, as well as α-smooth muscle actin (α-SMA) protein in liver tissues. Conversely, the mice displayed a decrease in these markers in the recovery phase. Remarkably, this model shows that the sterile liver injury following elevated hepatocyte apoptosis is associated with an increase in myeloid cells in the liver. Within 7 days post-Dox administration, the liver of Dox-treated 3xTg-iHAP mice displays a normal histological structure, indicating the completion of wound healing. Together, we established a novel mouse model of injury and regeneration induced by hepatocyte apoptosis. This tool provides a robust in vivo platform for studying the pathophysiology of sterile liver inflammation, regeneration, and new therapeutic interventions for liver diseases.<b>NEW & NOTEWORTHY</b> Bu et al. present a triple-transgenic mouse model, namely, 3xTg-iHAP mice that are engineered to explore hepatocyte apoptosis-triggered sterile liver injury and regeneration. This model demonstrates a full spectrum of liver wound-healing responses from asymptomatic apoptosis to injury, myeloid cell-dominant sterile inflammation, and repair after induction of hepatocyte-specific apoptosis. The robust nature of this model makes it an invaluable in vivo tool for studying sterile liver inflammation, regeneration, and new therapeutic strategies.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G499-G512"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892705","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":"Endogenous glucocorticoids are required for normal macrophage activation and gastric <i>Helicobacter pylori</i> immunity.","authors":"Stuti Khadka, Sebastian A Dziadowicz, Xiaojiang Xu, Lei Wang, Gangqing Hu, Javier A Carrero, Richard J DiPaolo, Jonathan T Busada","doi":"10.1152/ajpgi.00114.2024","DOIUrl":"10.1152/ajpgi.00114.2024","url":null,"abstract":"<p><p>Glucocorticoids are steroid hormones well known for their potent anti-inflammatory effects. However, their immunomodulatory properties are multifaceted. Increasing evidence suggests that glucocorticoid signaling promotes effective immunity and that disruption of glucocorticoid signaling impairs immune function. In this study, we conditionally deleted the glucocorticoid receptor (GR) in the myeloid lineage using the <i>LysM-Cre</i> driver (myGRKO). We examined the impact on macrophage activation and gastric immune responses to <i>Helicobacter pylori</i>, the best-known risk factor of gastric cancer. Our results indicate that, compared with wild type (WT), glucocorticoid receptor knockout (GRKO) macrophages exhibited higher expression of proinflammatory genes in steroid-free conditions. However, when challenged in vivo, GRKO macrophages exhibited aberrant chromatin landscapes and impaired proinflammatory gene expression profiles. Moreover, gastric colonization with <i>H. pylori</i> revealed impaired gastric immune responses and reduced T cell recruitment in myGRKO mice. As a result, myGRKO mice were protected from atrophic gastritis and pyloric metaplasia development. These results demonstrate a dual role for glucocorticoid signaling in preparing macrophages to respond to bacterial infection but limiting their pathogenic activation. In addition, our results support that macrophages are critical for gastric <i>H. pylori</i> immunity.<b>NEW & NOTEWORTHY</b> Signaling by endogenous glucocorticoids primes macrophages toward more robust responses to pathogens. Disruption of glucocorticoid signaling caused dysregulation of the chromatin landscape, blunted proinflammatory gene activation upon bacterial challenge, and impaired the gastric inflammatory response to <i>Helicobacter pylori</i> infection.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G531-G544"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747166","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":"Functional involvement of the sternohyoid muscle during breathing and swallowing in rats.","authors":"Nobuaki Saka, Titi Chotirungsan, Midori Yoshihara, Charng-Rong Pan, Yuhei Tsutsui, Nozomi Dewa, Jin Magara, Takanori Tsujimura, Makoto Inoue","doi":"10.1152/ajpgi.00138.2024","DOIUrl":"10.1152/ajpgi.00138.2024","url":null,"abstract":"<p><p>The sternohyoid muscle depresses the hyoid bone, but it is unclear whether the muscle contributes to respiratory and swallowing mechanisms. This study aimed to clarify whether the sternohyoid muscle participates in the respiration and swallowing reflex and how the activity is modulated in two conditions: with airway stenosis and with a fixed sternohyoid muscle length. Electromyographic activity in the sternohyoid, digastric, thyrohyoid, and diaphragm muscles was recorded in anesthetized rats. The sternohyoid muscle activity was observed in the inspiratory phase and during swallowing, and was well coordinated with digastric and thyrohyoid muscle activity. With airway stenosis, the respiratory activity per respiratory cycle was facilitated in all assessed muscles but the facilitation of activity per second occurred only in the digastric, thyrohyoid, and sternohyoid muscles. With airway stenosis, the swallowing activity was facilitated only in the digastric muscle but not in the thyrohyoid and sternohyoid muscles. Swallowing activity was not observed in the sternohyoid muscle in the condition with the sternohyoid muscle length fixed, although increased inspiratory activity remained. The current results suggest that <i>1</i>) the sternohyoid muscle is slightly activated in the inspiratory phase, <i>2</i>) the effect of airway stenosis on respiratory function may differ between the upper airway muscles and diaphragm, and <i>3</i>) swallowing activity in the sternohyoid muscle is not dominantly controlled by the swallowing central pattern generator but instead occurs as a myotatic reflex.<b>NEW & NOTEWORTHY</b> We found that the sternohyoid muscle was activated in the inspiratory phase. However, increased airway resistance had different effects on the extrathoracic muscles than on the diaphragm. The swallowing activity of the sternohyoid disappeared when the muscle length was fixed. These findings suggest that the sternohyoid muscle may be activated not by the swallowing central pattern generator but as a myotatic reflex.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G598-G607"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892707","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":"Increased activity of epithelial Cdc42 Rho GTPase and tight junction permeability in the Cftr knockout intestine.","authors":"Rowena A Woode, Ashlee M Strubberg, Jinghua Liu, Nancy M Walker, Lane L Clarke","doi":"10.1152/ajpgi.00211.2022","DOIUrl":"10.1152/ajpgi.00211.2022","url":null,"abstract":"<p><p>Increased intestinal permeability is a manifestation of cystic fibrosis (CF) in people with CF (pwCF) and in CF mouse models. CF transmembrane conductance regulator knockout (Cftr KO) mouse intestine exhibits increased proliferation and Wnt/β-catenin signaling relative to wild-type mice (WT). Since the Rho GTPase Cdc42 plays a central role in intestinal epithelial proliferation and tight junction remodeling, we hypothesized that Cdc42 may be altered in the Cftr KO crypts. Immunofluorescence showed distinct tight junction localization of Cdc42 in Cftr KO fresh crypts and enteroids, the latter indicating an epithelial-autonomous feature. Quantitative PCR and immunoblots revealed similar expression of Cdc42 in the Cftr KO crypts/enteroids relative to WT, whereas pulldown assays showed increased GTP-bound (active) Cdc42 in proportion to total Cdc42 in Cftr KO enteroids. Cdc42 activity in the Cftr KO and WT enteroids could be reduced by inhibition of the Wnt transducer Disheveled. With the use of a dye permeability assay, Cftr KO enteroids exhibited increased paracellular permeability to 3 kDa dextran relative to WT. Leak permeability and Cdc42 tight junction localization were reduced to a greater extent by inhibition of Wnt/β-catenin signaling with endo-IWR1 in Cftr KO relative to WT enteroids. Increased proliferation or inhibition of Cdc42 activity with ML141 in WT enteroids had no effect on permeability. In contrast, inhibition of Cdc42 with ML141 increased permeability to both 3 kDa dextran and tight junction impermeant 500 kDa dextran in Cftr KO enteroids. These data suggest that increased constitutive Cdc42 activity may alter the stability of paracellular permeability in Cftr KO crypt epithelium.<b>NEW & NOTEWORTHY</b> Increased tight junction localization and GTP-bound activity of the Rho GTPase Cdc42 was identified in small intestinal crypts and enteroids of cystic fibrosis (CF) transmembrane conductance regulator knockout (Cftr KO) mice. The increase in epithelial Cdc42 activity was associated with increased Wnt signaling. Paracellular flux of an uncharged solute (3 kDa dextran) in Cftr KO enteroids indicated a moderate leak permeability under basal conditions that was strongly exacerbated by Cdc42 inhibition. These findings suggest increased activity of Cdc42 in the Cftr KO intestine underlies alterations in intestinal permeability.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G545-G557"},"PeriodicalIF":3.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892656","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":"Mechanical stress, connective tissue growth factor, and intestinal fibrosis.","authors":"Sumei Liu","doi":"10.1152/ajpgi.00224.2024","DOIUrl":"https://doi.org/10.1152/ajpgi.00224.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118825","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":"Muscle protein catabolism and splanchnic arginine consumption drive arginine dysregulation during <i>Pseudomonas Aeruginosa</i> induced early acute sepsis in swine.","authors":"Sarah A Rice, Gabriella A M Ten Have, Marielle P K J Engelen, Nicolaas E P Deutz","doi":"10.1152/ajpgi.00257.2023","DOIUrl":"10.1152/ajpgi.00257.2023","url":null,"abstract":"<p><p>Human sepsis is characterized by increased protein breakdown and changes in arginine and citrulline metabolism. However, it is unclear whether this is caused by changes in transorgan metabolism. We therefore studied in a <i>Pseudomonas aeruginosa</i> induced pig sepsis model the changes in protein and arginine related metabolism on whole body (Wb) and transorgan level. We studied 22 conscious pigs for 18 hours during sepsis, induced by infusing live bacteria (<i>Pseudomonas aeruginosa)</i> or after placebo infusion (control). We used stable isotope tracers to measure Wb and skeletal muscle protein synthesis and breakdown, as well as Wb, splanchnic, skeletal muscle, hepatic and portal drained viscera (PDV) arginine and citrulline disposal and production rates. During sepsis, arginine Wb production (p=0.0146), skeletal muscle release (p=0.0035) and liver arginine uptake were elevated (p=0.0031). Wb <i>de novo</i> arginine synthesis, citrulline production, and transorgan PDV release of citrulline, glutamine and arginine did not differ between sepsis and controls. However, Wb (p<0.0001) and muscle (p<0.001) protein breakdown were increased, suggesting that the enhanced arginine production is predominantly derived from muscle breakdown in sepsis. In conclusion, live-bacterium sepsis increases muscle arginine release and liver uptake, mirroring previous pig endotoxemia studies. In contrast to observations in humans, acute live-bacterium sepsis in pigs does not change citrulline production or arterial arginine concentration. We therefore conclude that the arginine dysregulation observed in human sepsis is possibly initiated by enhanced protein catabolism and splanchnic arginine catabolism, while decreased arterial arginine concentration and citrulline metabolism may require more time to fully manifest in patients.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11559638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118764","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":"Targeting serotonin signaling in the gut to limit colitis via 5-HT₇ receptor antagonism.","authors":"Michael A Schumacher","doi":"10.1152/ajpgi.00181.2024","DOIUrl":"10.1152/ajpgi.00181.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G454-G455"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141791700","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":"Animal models with characteristics of irritable bowel syndrome with diarrhea: current applications and future perspectives.","authors":"Jinfeng Chen, Tingting Zhang, Yang Liu, Xueqian Dong, Jianjun Liu","doi":"10.1152/ajpgi.00060.2024","DOIUrl":"10.1152/ajpgi.00060.2024","url":null,"abstract":"<p><p>Irritable bowel syndrome with diarrhea (IBS-D) is a common intestinal condition that significantly impacts work efficiency and quality of life. The use of animal models is crucial for delving into the pathophysiology of IBS-D and exploring therapeutic options. However, a wide variety of animal models for IBS-D has been used in previous studies, posing a considerable challenge for researchers in selecting a suitable model. In this review, using the Web of Science database, we searched IBS-D-related research spanning from 2014 to 2023; described the differences in animal strains and modeling methods among various IBS-D features recapitulating models; summarized the frequency of model usage, pathogenesis, and pathological characteristics of these models; and discussed their current applications, limitations, and future perspectives. The objective is to offer theoretical guidance for future researchers, aiding them in choosing suitable animal models based on their experimental designs.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G360-G378"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619094","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":"Surface mapping of gastric motor functions using MRI: a comparative study between humans and rats.","authors":"Xiaokai Wang, Fatimah Alkaabi, Minkyu Choi, Madeleine R Di Natale, Ulrich M Scheven, Douglas C Noll, John B Furness, Zhongming Liu","doi":"10.1152/ajpgi.00045.2024","DOIUrl":"10.1152/ajpgi.00045.2024","url":null,"abstract":"<p><p>The stomach's ability to store, mix, propel, and empty its content requires highly coordinated motor functions. However, current diagnostic tools cannot simultaneously assess these motor processes. This study aimed to use magnetic resonance imaging (MRI) to map multifaceted gastric motor functions, including accommodation, tonic and peristaltic contractions, and emptying, through a single noninvasive experiment for both humans and rats. Ten humans and 10 Sprague-Dawley rats consumed MRI-visible semisolid meals and underwent MRI scans. We used a surface model to analyze MRI data, capturing the deformation of the stomach wall on ingestion or during digestion. We inferred muscle activity, mapped motor processes, parcellated the stomach into functional regions, and revealed cross-species distinctions. In humans, both the fundus and antrum distended postmeal, followed by sustained tonic contractions to regulate intragastric pressure. Peristaltic contractions initiated from the distal fundus, including three concurrent wavefronts oscillating at 3.3 cycles/min and traveling at 1.7 to 2.9 mm/s. These motor functions facilitated linear gastric emptying with a 61-min half-time. In contrast, rats exhibited peristalsis from the midcorpus, showing two wavefronts oscillating at 5.0 cycles/min and traveling at 0.4 to 0.9 mm/s. For both species, motility features allowed functional parcellation of the stomach along a midcorpus division. This study maps region- and species-specific gastric motor functions. We demonstrate the value of MRI with surface modeling in understanding gastric physiology and its potential to become a new standard for clinical and preclinical investigations of gastric disorders at both individual and group levels.<b>NEW & NOTEWORTHY</b> A novel MRI technique can visualize how the stomach accommodates, mixes, and propels food for digestion in humans and animals alike. Digital models of gastric MRI reveal the functional maps, organization, and distinction of the stomach across individuals and species. This technique holds the unique potential to advance basic and clinical studies of functional gastric disorders.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G345-G359"},"PeriodicalIF":3.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445212","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}