{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:18:12Z","timestamp":1788362292831,"version":"build-2803163510"},"reference-count":53,"publisher":"American Chemical Society (ACS)","issue":"3","license":[{"start":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T00:00:00Z","timestamp":1610496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100004919","name":"King Abdulaziz City for Science and Technology","doi-asserted-by":"publisher","award":["13-MED 920-02"],"award-info":[{"award-number":["13-MED 920-02"]}],"id":[{"id":"10.13039\/501100004919","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The thyroid gland and thyroid hormones control a multitude of homeostatic functions including maintenance of fluid and electrolyte balance and normal functioning of the kidneys. Thyroid dysfunction alters the sytemic hemodynamic and metabolic balance, thereby affecting the kidney. In this study, we aimed to identify and characterize the urinary proteome of the patients with hypothyroidism. An untargeted proteomic approach with network analysis was used to identify changes in total urinary proteome in patients with newly diagnosed overt hypothyroidism. Urine samples were collected from nine age-matched patients\u2019 before and after l-thyroxine treatment. Differences in the abundance of urinary proteins between hypothyroid and euthyroid states were determined using a two-dimensional difference in gel electrophoresis (2D-DIGE) coupled to matrix-assisted laser desorption and ionization time-of-flight (MALDI TOF) mass spectrometry. Alterations in the abundance of urinary proteins, analyzed by Progenesis software, revealed statistically significant differential abundance in a total of 49 spots corresponding to 42 proteins, 28 up and 14 down (\u22651.5-fold change, analysis of variance (ANOVA), p \u2264 0.05). The proteins identified in the study are known to regulate processes related to transport, acute phase response, oxidative stress, generation of reactive oxygen species, cellular proliferation, and endocytosis. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of pathways related to amino acid metabolism, molecular transport, and small-molecule biochemistry and involved the MAPK kinase, vascular endothelial growth factor (VEGF), PI3 kinase\/Akt, protein kinase C (PKC), signaling pathways. The identified proteins were involved in the regulation of thyroglobulin (Tg) and thyrotropin (TSH) metabolism. Alterations in their levels indicate the presence of a compensatory mechanism aimed at increasing the regulation of Tg in the hypothyroid state.<\/jats:p>","DOI":"10.1021\/acsomega.0c05686","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T23:43:02Z","timestamp":1610667782000},"page":"2367-2378","source":"Crossref","is-referenced-by-count":9,"title":["Identification of Protein Changes in the Urine of\nHypothyroid Patients Treated with Thyroxine Using Proteomics Approach"],"prefix":"10.1021","volume":"6","author":[{"given":"Afshan","family":"Masood","sequence":"first","affiliation":[{"name":"King Saud University , , ,","place":["Riyadh, Saudi Arabia, 11461"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-2959","authenticated-orcid":true,"given":"Hicham","family":"Benabdelkamel","sequence":"additional","affiliation":[{"name":"King Saud University , , ,","place":["Riyadh, Saudi Arabia, 11461"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar A.","family":"Jammah","sequence":"additional","affiliation":[{"name":"King Saud University , , ,","place":["Riyadh, Saudi Arabia, 12372"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishah A.","family":"Ekhzaimy","sequence":"additional","affiliation":[{"name":"King Saud University , , ,","place":["Riyadh, Saudi Arabia, 12372"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assim A.","family":"Alfadda","sequence":"additional","affiliation":[{"name":"King Saud University , , ,","place":["Riyadh, Saudi Arabia, 11461"]},{"name":"King Saud University , , ,","place":["Riyadh, Saudi Arabia, 12372"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"2026090210462130900_cit1","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1530\/EJE-08-0837","article-title":"Thyroid dysfunction\nand kidney disease","volume":"160","author":"Iglesias","year":"2009","journal-title":"Eur. J. Endocrinol."},{"key":"2026090210462130900_cit2","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1210\/jc.2012-1663","article-title":"Preservation\nof\nrenal function by thyroid hormone replacement therapy in chronic kidney\ndisease patients with subclinical hypothyroidism","volume":"97","author":"Shin","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2026090210462130900_cit3","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-42905-4","article-title":"The relationship between thyroid\ndysfunction and nephrotic syndrome: a clinicopathological study","volume":"9","author":"Li","year":"2019","journal-title":"Sci. Rep."},{"key":"2026090210462130900_cit4","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1093\/ndt\/gfh096","article-title":"Correction of metabolic acidosis\nimproves thyroid and growth hormone axes in haemodialysis patients","volume":"19","author":"Wiederkehr","year":"2004","journal-title":"Nephrol., Dial., Transplant."},{"key":"2026090210462130900_cit5","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1055\/s-2007-979105","article-title":"Plasma\nrenin and aldosterone in thyroid diseases","volume":"29","author":"Asmah","year":"1997","journal-title":"Horm.\nMetab. Res."},{"key":"2026090210462130900_cit6","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1172\/JCI106936","article-title":"Renal handling\nof sodium and water in the hypothyroid rat. Clearance and micropuncture\nstudies","volume":"51","author":"Michael","year":"1972","journal-title":"J. Clin. Invest."},{"key":"2026090210462130900_cit7","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/0024-3205(82)90279-X","article-title":"Changes in\nglomerulotubular dimensions, single nephron glomerular filtration\nrates and the renin-angiotensin system in hypothyroid rats","volume":"30","author":"Bradley","year":"1982","journal-title":"Life Sci."},{"key":"2026090210462130900_cit8","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1111\/j.1365-2265.1983.tb00601.x","article-title":"Mild hypothyroidism\nand oedema: evidence for increased\ncapillary permeability to protein","volume":"18","author":"Wheatley","year":"1983","journal-title":"Clin. Endocrinol."},{"key":"2026090210462130900_cit9","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1002\/pmic.200401012","article-title":"Renal and urinary proteomics:\ncurrent applications\nand challenges","volume":"5","author":"Thongboonkerd","year":"2005","journal-title":"Proteomics"},{"key":"2026090210462130900_cit10","doi-asserted-by":"publisher","first-page":"4085","DOI":"10.1021\/acs.jproteome.9b00503","article-title":"Mass Spectrometry-Based\nPlasma Proteomics: Considerations from Sample Collection to Achieving\nTranslational Data","volume":"18","author":"Ignjatovic","year":"2019","journal-title":"J. Proteome Res."},{"key":"2026090210462130900_cit11","doi-asserted-by":"publisher","DOI":"10.3390\/ht7030027","article-title":"Obesity Proteomics: An Update on\nthe Strategies and Tools Employed in the Study of Human Obesity","volume":"7","author":"Masood","year":"2018","journal-title":"High-Throughput"},{"key":"2026090210462130900_cit12","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-9-r80","article-title":"The human\nurinary proteome contains more than 1500 proteins, including a large\nproportion of membrane proteins","volume":"7","author":"Adachi","year":"2006","journal-title":"Genome Biol."},{"key":"2026090210462130900_cit13","doi-asserted-by":"publisher","first-page":"2734","DOI":"10.1021\/pr2003038","article-title":"A comprehensive\nmap of the human urinary proteome","volume":"10","author":"Marimuthu","year":"2011","journal-title":"J. Proteome\nRes."},{"key":"2026090210462130900_cit14","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1074\/mcp.M700394-MCP200","article-title":"Urinary\nproteomic biomarkers in coronary artery disease","volume":"7","author":"Zimmerli","year":"2008","journal-title":"Mol. Cell. Proteomics"},{"key":"2026090210462130900_cit15","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-016-0246-y","article-title":"Urine proteomics\nin\nthe diagnosis of stable angina","volume":"16","author":"Neisius","year":"2016","journal-title":"BMC Cardiovasc.\nDisord."},{"key":"2026090210462130900_cit16","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.3892\/mmr.2019.9911","article-title":"Potential\nurine biomarkers for gestational hypertension and preeclampsia","volume":"19","author":"Guo","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"2026090210462130900_cit17","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201800174","article-title":"Urinary Peptidomic Biomarker for\nPersonalized Prevention and Treatment of Diastolic Left Ventricular\nDysfunction","volume":"13","author":"Zhang","year":"2019","journal-title":"Proteomics: Clin. Appl."},{"key":"2026090210462130900_cit18","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.diabres.2018.02.034","article-title":"Urinary afamin levels are associated\nwith the progression of diabetic nephropathy","volume":"147","author":"Kaburagi","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"2026090210462130900_cit19","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201700135","article-title":"Discovery\nand Validation of Novel Protein Biomarkers in Ovarian Cancer Patient\nUrine","volume":"12","author":"Sandow","year":"2018","journal-title":"Proteomics: Clin. Appl."},{"key":"2026090210462130900_cit20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.critrevonc.2017.08.002","article-title":"Urinary biomarkers\nin prostate cancer detection and monitoring progression","volume":"118","author":"Wu","year":"2017","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"2026090210462130900_cit21","doi-asserted-by":"publisher","first-page":"40412","DOI":"10.18632\/oncotarget.16341","article-title":"Urinary RKIP\/p-RKIP\nis a potential diagnostic and prognostic marker of clear cell renal\ncell carcinoma","volume":"8","author":"Papale","year":"2017","journal-title":"Oncotarget"},{"key":"2026090210462130900_cit22","doi-asserted-by":"publisher","first-page":"38517","DOI":"10.18632\/oncotarget.15870","article-title":"Identification of urine\nbiomarkers\nassociated with lung adenocarcinoma","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"2026090210462130900_cit23","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.1002\/pmic.201600015","article-title":"Urinary proteome alterations in HER2 enriched breast\ncancer revealed by multipronged quantitative proteomics","volume":"16","author":"Gajbhiye","year":"2016","journal-title":"Proteomics"},{"key":"2026090210462130900_cit24","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1097\/MED.0000000000000275","article-title":"The interaction\nbetween thyroid and kidney disease: an overview of the evidence","volume":"23","author":"Rhee","year":"2016","journal-title":"Curr. Opin. Endocrinol., Diabetes Obes."},{"key":"2026090210462130900_cit25","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19010088","article-title":"Differences\nin the Plasma Proteome of Patients with Hypothyroidism before and\nafter Thyroid Hormone Replacement: A Proteomic Analysis","volume":"19","author":"Alfadda","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2026090210462130900_cit26","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0003-2697(84)90782-6","article-title":"A method for the\nquantitative recovery of protein in\ndilute solution in the presence of detergents and lipids","volume":"138","author":"Wessel","year":"1984","journal-title":"Anal. Biochem."},{"key":"2026090210462130900_cit27","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194905","article-title":"A Proteomics-Based\nApproach Reveals Differential Regulation of Urine Proteins between\nMetabolically Healthy and Unhealthy Obese Patients","volume":"20","author":"Benabdelkamel","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"2026090210462130900_cit28","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1016\/j.exger.2013.07.008","article-title":"Proteomic analysis of mature adipocytes\nfrom obese patients in relation to aging","volume":"48","author":"Alfadda","year":"2013","journal-title":"Exp.\nGerontol."},{"key":"2026090210462130900_cit29","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.mce.2014.11.021","article-title":"Mature\nadipocyte proteome reveals\ndifferentially altered protein abundances between lean, overweight\nand morbidly obese human subjects","volume":"401","author":"Benabdelkamel","year":"2015","journal-title":"Mol. Cell.\nEndocrinol."},{"key":"2026090210462130900_cit30","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1651-z","article-title":"Establishment of urinary\nexosome-like vesicles isolation protocol for FHHNC patients and evaluation\nof different exosomal RNA extraction methods","volume":"16","author":"Vall-Palomar","year":"2018","journal-title":"J. Transl. Med."},{"key":"2026090210462130900_cit31","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1016\/j.jprot.2009.12.003","article-title":"2D-electrophoresis\nand the urine proteome map: where do we stand?","volume":"73","author":"Candiano","year":"2010","journal-title":"J. Proteomics"},{"key":"2026090210462130900_cit32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/978-1-4684-5260-0_14","article-title":"Thyroid Hormone-Binding\nPlasma Proteins","volume-title":"Frontiers in Thyroidology","author":"Hennemann","year":"1986"},{"key":"2026090210462130900_cit33","doi-asserted-by":"publisher","first-page":"2116","DOI":"10.1210\/endo.133.5.8404661","article-title":"Thyroxine transport to the brain:\nrole of protein synthesis by the choroid plexus","volume":"133","author":"Southwell","year":"1993","journal-title":"Endocrinology"},{"key":"2026090210462130900_cit34","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1055\/s-0035-1564199","article-title":"Retinol Binding Protein-4 and Adiponectin\nLevels in Thyroid Overt and Subclinical Dysfunction","volume":"124","author":"Kokkinos","year":"2016","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"2026090210462130900_cit35","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1002\/elps.201800124","article-title":"Comparison of protein\nprecipitation methods from adipose tissue using difference gel electrophoresis","author":"Benabdelkamel","year":"2018","journal-title":"Electrophoresis"},{"key":"2026090210462130900_cit36","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1016\/j.nutres.2014.06.007","article-title":"Iron deficiency\nwithout anemia causes maternal hypothyroxinemia in pregnant rats","volume":"34","author":"Hu","year":"2014","journal-title":"Nutr. Res."},{"key":"2026090210462130900_cit37","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1093\/jn\/132.7.1951","article-title":"Iron deficiency\nanemia reduces thyroid peroxidase activity in rats","volume":"132","author":"Hess","year":"2002","journal-title":"J. Nutr."},{"key":"2026090210462130900_cit38","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1507\/endocrj.K10E-333","article-title":"Endothelial\ndysfunction and low grade chronic inflammation in subclinical hypothyroidism\ndue to autoimmune thyroiditis","volume":"58","author":"Tu\u0308remen","year":"2011","journal-title":"Endocr. J."},{"key":"2026090210462130900_cit39","doi-asserted-by":"publisher","first-page":"629","DOI":"10.2337\/dc06-2056","article-title":"Proteomic identification\nof urinary biomarkers of diabetic nephropathy","volume":"30","author":"Rao","year":"2007","journal-title":"Diabetes Care"},{"key":"2026090210462130900_cit40","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1093\/glycob\/9.8.833","article-title":"Vesicular-integral\nmembrane protein, VIP36, recognizes high-mannose type glycans containing\n\u03b11\u2192 2 mannosyl residues in MDCK cells","volume":"9","author":"Hara-Kuge","year":"1999","journal-title":"Glycobiology"},{"key":"2026090210462130900_cit41","doi-asserted-by":"crossref","first-page":"4485","DOI":"10.1242\/jcs.114.24.4485","article-title":"Nesprins:\na novel family of spectrin-repeat-containing proteins that localize\nto the nuclear membrane in multiple tissues","volume":"114","author":"Zhang","year":"2001","journal-title":"J. Cell Sci."},{"key":"2026090210462130900_cit42","doi-asserted-by":"publisher","first-page":"6276","DOI":"10.3892\/mmr.2017.7329","article-title":"Proteomic\nprofilebased screening of potential protein biomarkers in the urine\nof patients with nephrotic syndrome","volume":"16","author":"Wang","year":"2017","journal-title":"Mol. Med.\nRep."},{"key":"2026090210462130900_cit43","doi-asserted-by":"publisher","first-page":"4272","DOI":"10.1021\/pr900363s","article-title":"High speed two-dimensional\nprotein separation without\ngel by isoelectric focusing-asymmetrical flow field flow fractionation:\napplication to urinary proteome","volume":"8","author":"Kim","year":"2009","journal-title":"J. Proteome\nRes."},{"key":"2026090210462130900_cit44","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1089\/thy.2016.0661","article-title":"A higher ratio of estradiol\nto testosterone is associated with autoimmune\nthyroid disease in males","volume":"27","author":"Chen","year":"2017","journal-title":"Thyroid"},{"key":"2026090210462130900_cit45","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.ejcb.2017.02.002","article-title":"Interdependence of thyroglobulin processing and thyroid hormone export\nin the mouse thyroid gland","volume":"96","author":"Weber","year":"2017","journal-title":"Eur. J. Cell Biol."},{"key":"2026090210462130900_cit46","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1210\/er.2015-1090","article-title":"Thyroglobulin From Molecular and Cellular Biology to\nClinical Endocrinology","volume":"37","author":"Di Jeso","year":"2016","journal-title":"Endocr. Rev."},{"key":"2026090210462130900_cit47","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1096\/fasebj.14.7.1005","article-title":"Covalent cross-linking\nof secreted\nbovine thyroglobulin by transglutaminase","volume":"14","author":"Saber-Lichtenberg","year":"2000","journal-title":"FASEB\nJ."},{"key":"2026090210462130900_cit48","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092792","article-title":"Glycosylation in the Thyroid Gland:\nVital Aspects of Glycoprotein Function in Thyrocyte Physiology and\nThyroid Disorders","volume":"19","author":"Zabczynska","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2026090210462130900_cit49","doi-asserted-by":"publisher","first-page":"15434","DOI":"10.1074\/jbc.M117.784447","article-title":"De novo triiodothyronine\nformation from thyrocytes activated by thyroid-stimulating hormone","volume":"292","author":"Citterio","year":"2017","journal-title":"J. Biol. Chem."},{"key":"2026090210462130900_cit50","doi-asserted-by":"publisher","first-page":"17061","DOI":"10.1074\/jbc.M809725200","article-title":"Human OS-9,\na lectin required for glycoprotein endoplasmic reticulum-associated\ndegradation, recognizes mannose-trimmed N-glycans","volume":"284","author":"Hosokawa","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2026090210462130900_cit51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116938","article-title":"H-Ras mediates the\ninhibitory effect of epidermal growth factor on the epithelial Na+\nchannel","volume":"10","author":"Lee","year":"2015","journal-title":"PLoS One"},{"key":"2026090210462130900_cit52","doi-asserted-by":"publisher","first-page":"4511","DOI":"10.3892\/ol.2018.7818","article-title":"Identification of a novel HRAS variant\nand its association with papillary thyroid carcinoma","volume":"15","author":"Dou","year":"2018","journal-title":"Oncol. Lett."},{"key":"2026090210462130900_cit53","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1158\/0008-5472.CAN-13-1617","article-title":"CRR9\/CLPTM1L regulates cell survival\nsignaling and is required for\nRas transformation and lung tumorigenesis","volume":"74","author":"James","year":"2014","journal-title":"Cancer\nRes."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c05686","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/6\/3\/2367\/67801175\/acsomega.0c05686.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/6\/3\/2367\/67801175\/acsomega.0c05686.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:47:09Z","timestamp":1788360429000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/6\/3\/2367\/421514\/Identification-of-Protein-Changes-in-the-Urine-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,13]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,1,13]]},"published-print":{"date-parts":[[2021,1,26]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c05686","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-16161\/v1","asserted-by":"object"}]},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,13]]}}}