{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T17:49:40Z","timestamp":1759600180164,"version":"3.41.2"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Thyroid hormone is critical during the development of vertebrates and affects the function of many organs and tissues, especially the intestine. Triiodothyronine (T<jats:sub>3<\/jats:sub>) is the active form and can bind to thyroid hormone nuclear receptors (TRs) to play a vital role in the development of vertebrates. The resistance to thyroid hormone \u03b1, as seen in patients, has been mimicked by the <jats:italic>Thra<\/jats:italic><jats:sup>E403X<\/jats:sup> mutation. To investigate the mechanisms underlying the effect of TR\u03b11 on intestinal development, the present study employed proteomic analysis to identify differentially expressed proteins (DEPs) in the distal ileum between homozygous <jats:italic>Thra<\/jats:italic><jats:sup>E403X\/E403X<\/jats:sup> and wild-type <jats:italic>Thra<\/jats:italic><jats:sup>+\/+<\/jats:sup> mice. A total of 1,189 DEPs were identified, including 603 upregulated and 586 downregulated proteins. Proteomic analysis revealed that the DEPs were highly enriched in the metabolic process, the developmental process, the transporter of the nutrients, and the intestinal immune system-related pathway. Of these DEPs, 20 proteins were validated by parallel reaction monitoring analysis. Our intestinal proteomic results provide promising candidates for future studies, as they suggest novel mechanisms by which TR\u03b11 may influence intestinal development, such as the transport of intestinal nutrients and the establishment of innate and adaptive immune barriers of the intestine.<\/jats:p>","DOI":"10.3389\/fendo.2022.773516","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T04:42:47Z","timestamp":1651120967000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Proteomic Analysis of the Intestinal Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Mutations"],"prefix":"10.3389","volume":"13","author":[{"given":"Yue","family":"Xi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyan","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochun","family":"Teng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiping","family":"Teng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2018.0340","article-title":"Thyroid Hormone Receptor Alpha Mutations Lead to Epithelial Defects in the Adult Intestine in a Mouse Model of Resistance to Thyroid Hormone","volume":"29","author":"Bao","year":"2019","journal-title":"Thyroid"},{"key":"B2","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13578-020-00411-5","article-title":"Thyroid Hormone Receptor Beta Is Critical for Intestinal Remodeling During Xenopus Tropicalis Metamorphosis","volume":"10","author":"Shibata","year":"2020","journal-title":"Cell Biosci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13578-015-0004-3","article-title":"A Requirement for Hedgehog Signaling in Thyroid Hormone-Induced Postembryonic Intestinal Remodeling","volume":"5","author":"Wen","year":"2015","journal-title":"Cell Biosci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-14-2-184","article-title":"Thyroid Hormone Receptors: Multiple Forms, Multiple Possibilities","volume":"14","author":"Lazar","year":"1993","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.02.012","article-title":"New Insights Into Thyroid Hormone Action","volume":"173","author":"Mendoza","year":"2017","journal-title":"Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00247","article-title":"The Nuclear Receptor Superfamily","volume":"116","author":"Robinson-Rechavi","year":"2003","journal-title":"J Cell Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.13.5712-5724.2005","article-title":"Coactivator Recruitment Is Essential for Liganded Thyroid Hormone Receptor to Initiate Amphibian Metamorphosis","volume":"25","author":"Paul","year":"2005","journal-title":"Mol Cell Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2005.11.030","article-title":"Thyroid Hormone Action at the Cellular, Genomic and Target Gene Levels","volume":"246","author":"Yen","year":"2006","journal-title":"Mol Cell Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19479","article-title":"Thyroid Hormone Action: A Binding Contract","volume":"112","author":"Lazar","year":"2003","journal-title":"J Clin Invest"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2014.143","article-title":"Thyroid Hormone Receptors and Resistance to Thyroid Hormone Disorders","volume":"10","author":"Ortiga-Carvalho","year":"2014","journal-title":"Nat Rev Endocrinol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/337659a0","article-title":"Inhibition of Thyroid Hormone Action by a Non-Hormone Binding c-erbA Protein Generated by Alternative mRNA Splicing","volume":"337","author":"Koenig","year":"1989","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/mend.11.9.9972","article-title":"Identification of Transcripts Initiated From an Internal Promoter in the c-erbA Alpha Locus That Encode Inhibitors of Retinoic Acid Receptor-Alpha and Triiodothyronine Receptor Activities","volume":"11","author":"Chassande","year":"1997","journal-title":"Mol Endocrinol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1210\/en.2015-1443","article-title":"Thyroid Hormone Receptor \u03b1 Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury","volume":"157","author":"Milanesi","year":"2016","journal-title":"Endocrinology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1248","article-title":"The Rat Thyroid Hormone Receptor (TR) Deltabeta3 Displays Cell-, TR Isoform-, and Thyroid Hormone Response Element-Specific Actions","volume":"148","author":"Harvey","year":"2007","journal-title":"Endocrinology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.22.8329-8342.2000","article-title":"Cloning and Characterization of Two Novel Thyroid Hormone Receptor Beta Isoforms","volume":"20","author":"Williams","year":"2000","journal-title":"Mol Cell Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.03.002","article-title":"Thyroid Hormone Regulation of Intestinal Epithelial Stem Cell Biology","volume":"459","author":"Frau","year":"2017","journal-title":"Mol Cell Endocrinol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i23.7142","article-title":"Molecular Aspects of Intestinal Calcium Absorption","volume":"21","author":"Diaz de Barboza","year":"2015","journal-title":"World J Gastroenterol"},{"key":"B18","article-title":"Research on the Sensitivity of the Thyroid Gland of the Tadpole (Rana Temporaria) to Thyreostimuline","volume":"154","author":"FABRE","year":"1960","journal-title":"C R Seances Soc Biol Fil"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.14.4412","article-title":"The T3R Alpha Gene Encoding a Thyroid Hormone Receptor Is Essential for Post-Natal Development and Thyroid Hormone Production","volume":"16","author":"Fraichard","year":"1997","journal-title":"EMBO J"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.14.4748-4760.2001","article-title":"Genetic Analysis Reveals Different Functions for the Products of the Thyroid Hormone Receptor Alpha Locus","volume":"21","author":"Gauthier","year":"2001","journal-title":"Mol Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0733","article-title":"Generation and Characterization of a New Resistance to Thyroid Hormone Mouse Model With Thyroid Hormone Receptor Alpha Gene Mutation","volume":"31","author":"Liang","year":"2021","journal-title":"Thyroid"},{"key":"B22","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.envint.2019.03.016","article-title":"Proteomic Analysis of the Reduction and Resistance Mechanisms of Shewanella Oneidensis MR-1 Under Long-Term Hexavalent Chromium Stress","volume":"127","author":"Gang","year":"2019","journal-title":"Environ Int"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.O112.020131","article-title":"Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics","volume":"11","author":"Peterson","year":"2012","journal-title":"Mol Cell Proteomics"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70501-9","article-title":"Involvement of T3Ralpha- and Beta-Receptor Subtypes in Mediation of T3 Functions During Postnatal Murine Intestinal Development","volume":"116","author":"Plateroti","year":"1999","journal-title":"Gastroenterology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1953","article-title":"Thyroid Hormone Receptor \u03b1 Controls Developmental Timing and Regulates the Rate and Coordination of Tissue-Specific Metamorphosis in Xenopus Tropicalis","volume":"158","author":"Wen","year":"2017","journal-title":"Endocrinology"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1210\/en.2016-1955","article-title":"Growth, Development, and Intestinal Remodeling Occurs in the Absence of Thyroid Hormone Receptor \u03b1 in Tadpoles of Xenopus Tropicalis","volume":"158","author":"Choi","year":"2017","journal-title":"Endocrinology"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0022","article-title":"Analysis of Thyroid Hormone Receptor \u03b1-Knockout Tadpoles Reveals That the Activation of Cell Cycle Program Is Involved in Thyroid Hormone-Induced Larval Epithelial Cell Death and Adult Intestinal Stem Cell Development During Xenopus Tropicalis Metamorphosis","volume":"31","author":"Tanizaki","year":"2021","journal-title":"Thyroid"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030536","article-title":"Thyroid Hormone Receptor Is Essential for Larval Epithelial Apoptosis and Adult Epithelial Stem Cell Development But Not Adult Intestinal Morphogenesis During Xenopus Tropicalis Metamorphosis","volume":"10","author":"Shibata","year":"2021","journal-title":"Cells"},{"key":"B29","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1210\/mend.16.1.0766","article-title":"Congenital Hypothyroid Pax8(-\/-) Mutant Mice Can Be Rescued by Inactivating the TRalpha Gene","volume":"16","author":"Flamant","year":"2002","journal-title":"Mol Endocrinol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13578-020-00429-9","article-title":"Intestinal Homeostasis: A Communication Between Life and Death","volume":"10","author":"Bao","year":"2020","journal-title":"Cell Biosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.199","article-title":"Cyclooxygenase-2-Dependent Phosphorylation of the Pro-Apoptotic Protein Bad Inhibits Tonicity-Induced Apoptosis in Renal Medullary Cells","volume":"80","author":"K\u00fcper","year":"2011","journal-title":"Kidney Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/science.1115035","article-title":"Caspases 3 and 7: Key Mediators of Mitochondrial Events of Apoptosis","volume":"311","author":"Lakhani","year":"2006","journal-title":"Science"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.1249361","article-title":"Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis","volume":"343","author":"Newton","year":"2014","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795-279","article-title":"Adenosine-Deaminase-Deficient Mice Die Perinatally and Exhibit Liver-Cell Degeneration, Atelectasis and Small Intestinal Cell Death","volume":"10","author":"Migchielsen","year":"1995","journal-title":"Nat Genet"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0567","article-title":"Influence of Thyroid Hormone and Thyroid Hormone Receptors in the Generation of Cerebellar Gamma-Aminobutyric Acid-Ergic Interneurons From Precursor Cells","volume":"148","author":"Manzano","year":"2007","journal-title":"Endocrinology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.03.048","article-title":"Triiodothyronine Promotes the Proliferation of Epicardial Progenitor Cells Through the MAPK\/ERK Pathway","volume":"486","author":"Deng","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"B37","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S0304-3940(00)01580-9","article-title":"In Vivo Regulation of Precursor Cells in the Subventricular Zone of Adult Rat Brain by Thyroid Hormone and Retinoids","volume":"295","author":"Giardino","year":"2000","journal-title":"Neurosci Lett"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbr042","article-title":"Phylogenetic-Based Propagation of Functional Annotations Within the Gene Ontology Consortium","volume":"12","author":"Gaudet","year":"2011","journal-title":"Brief Bioinform"},{"key":"B39","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.trsl.2015.08.009","article-title":"Aging-Associated Changes in Oxidative Stress, Cell Proliferation, and Apoptosis Are Prevented in the Prostate of Transgenic Rats Overexpressing Regucalcin","volume":"166","author":"Vaz","year":"2015","journal-title":"Transl Res"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.gene.2007.05.008","article-title":"Differential Gene Expression and Dependence on Thyroid Hormones of Two Glyceraldehyde-3-Phosphate Dehydrogenases in the Flatfish Senegalese Sole (Solea Senegalensis Kaup)","volume":"400","author":"Manchado","year":"2007","journal-title":"Gene"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1410169","article-title":"Norepinephrine, Tri-Iodothyronine and Insulin Upregulate Glyceraldehyde-3-Phosphate Dehydrogenase mRNA During Brown Adipocyte Differentiation","volume":"141","author":"Barroso","year":"1999","journal-title":"Eur J Endocrinol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/ng1197-327","article-title":"Early Diabetes and Abnormal Postnatal Pancreatic Islet Development in Mice Lacking Glut-2","volume":"17","author":"Guillam","year":"1997","journal-title":"Nat Genet"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.53.030191.003025","article-title":"Structure-Function Relationship of Na,K-ATPase","volume":"53","author":"Horisberger","year":"1991","journal-title":"Annu Rev Physiol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2009","article-title":"Biology of Human Sodium Glucose Transporters","volume":"91","author":"Wright","year":"2011","journal-title":"Physiol Rev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1818504116","article-title":"Convergent Gene Losses Illuminate Metabolic and Physiological Changes in Herbivores and Carnivores","volume":"116","author":"Hecker","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.40.24698","article-title":"Hepatocellular and Hepatic Peroxisomal Alterations in Mice With a Disrupted Peroxisomal Fatty Acyl-Coenzyme A Oxidase Gene","volume":"271","author":"Fan","year":"1996","journal-title":"J Biol Chem"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303422200","article-title":"Pancreatic Triglyceride Lipase Deficiency Minimally Affects Dietary Fat Absorption But Dramatically Decreases Dietary Cholesterol Absorption in Mice","volume":"278","author":"Huggins","year":"2003","journal-title":"J Biol Chem"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408638200","article-title":"Identification of LAT4, a Novel Amino Acid Transporter With System L Activity","volume":"280","author":"Bodoy","year":"2005","journal-title":"J Biol Chem"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.283960","article-title":"Essential Amino Acid Transporter Lat4 (Slc43a2) Is Required for Mouse Development","volume":"593","author":"Guetg","year":"2015","journal-title":"J Physiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1113\/JP280234","article-title":"Tissue-Specific Deletion of Mouse Basolateral Uniporter LAT4 (Slc43a2) Reveals Its Crucial Role in Small Intestine and Kidney Amino Acid Transport","volume":"598","author":"Rajendran","year":"2020","journal-title":"J Physiol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.001","article-title":"The Biology of Intestinal Immunoglobulin A Responses","volume":"28","author":"Cerutti","year":"2008","journal-title":"Immunity"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<2871::AID-IMMU2871>3.0.CO;2-B","article-title":"Altered Major Histocompatibility Complex Class II Peptide Loading in H2-O-Deficient Mice","volume":"30","author":"Perraudeau","year":"2000","journal-title":"Eur J Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6348","article-title":"The Impact of H2-DM on Humoral Immune Responses","volume":"167","author":"Alfonso","year":"2001","journal-title":"J Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81030-2","article-title":"H2-M Mutant Mice Are Defective in the Peptide Loading of Class II Molecules, Antigen Presentation, and T Cell Repertoire Selection","volume":"84","author":"Martin","year":"1996","journal-title":"Cell"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12694","article-title":"A Novel Spontaneous Mutation in the TAP2 Gene Unravels Its Role in Macrophage Survival","volume":"150","author":"Lapenna","year":"2017","journal-title":"Immunology"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.5.1723","article-title":"Analysis of Natural Killer Cells in TAP2-Deficient Patients: Expression of Functional Triggering Receptors and Evidence for the Existence of Inhibitory Receptor(s) That Prevent Lysis of Normal Autologous Cells","volume":"99","author":"Vitale","year":"2002","journal-title":"Blood"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050430","article-title":"Sequence, Linkage to H2-K, and Function of Mouse Tapasin in MHC Class I Assembly","volume":"48","author":"Grandea","year":"1998","journal-title":"Immunogenetics"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.01.00228801","article-title":"Lung Mucosal Immunity: Immunoglobulin-A Revisited","volume":"18","author":"Pilette","year":"2001","journal-title":"Eur Respir J"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.773516\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T04:42:51Z","timestamp":1651120971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.773516\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,28]]},"references-count":58,"alternative-id":["10.3389\/fendo.2022.773516"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.773516","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2022,4,28]]},"article-number":"773516"}}