{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T10:39:01Z","timestamp":1787740741620,"version":"build-2784847793"},"reference-count":60,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Mitochondrial dysfunction in the thyroid due to defective mitophagy has been observed in lymphocytic thyroiditis (LT). However, the effect of impaired mitophagy on the pathogenesis of LT is not well understood. The aim of this study is to investigate the role of mitophagy dysregulation in the thyroid gland.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We analyzed RNA sequencing data of human thyroid glands with\/without LT from Genotype-Tissue Expression (GTEx;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 653) and performed RNA sequencing in thyroid glands of phosphatase and tensin homolog-induced putative protein kinase 1 (\n                      <jats:italic toggle=\"yes\">Pink1<\/jats:italic>\n                      ) knock-out and wild-type mice. We evaluated the phenotypic and histopathologic characteristics of the human (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      = 16) and mouse thyroids. Additionally, we assessed cell proliferation, reactive oxygen species (ROS) production, and cytokine secretion of human thyroid epithelial cells (HTori-3) treated with\n                      <jats:italic toggle=\"yes\">PINK1<\/jats:italic>\n                      siRNA or a mitophagy inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We found that expression of\n                      <jats:italic toggle=\"yes\">PINK1<\/jats:italic>\n                      , a key regulator of mitophagy, was compromised in human thyroids with LT. Thyroid glands of\n                      <jats:italic toggle=\"yes\">Pink1<\/jats:italic>\n                      -deficient mice exhibited increased inflammatory responses and nodular hyperplasia. Furthermore, mitophagy defects led to the production of pro-inflammatory cytokines and ROS in thyroid cells, resulting in immune cell recruitment. Notably, these mitophagy defects upregulated both the RNA expression and protein secretion of amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand, in thyroid cells, while decreasing the protein expression of cAMP response element-binding protein (CREB), a transcription factor that suppresses AREG transcription. Finally, we demonstrated that aberrant cell proliferation in thyroid cells, driven by mitophagy defects, was mitigated after treatment with cetuximab, an EGFR inhibitor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In this study, we observed that mitophagy defects in the thyroid not only intensify inflammation through the accumulation of ROS, cytokine production, and immune cell recruitment but also contribute to hyperplasia via the EGFR pathway, facilitated by increased secretion of AREG from thyroid cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2024.0125","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:24:37Z","timestamp":1728879877000},"page":"1401-1413","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Mitophagy Defects Exacerbate Inflammation and Aberrant Proliferation in Lymphocytic Thyroiditis"],"prefix":"10.1177","volume":"34","author":[{"given":"Han Sai","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea."},{"name":"Department of Biomedical Science, Graduate School, CHA University, Seongnam, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea."},{"name":"Department of Biomedical Science, Graduate School, CHA University, Seongnam, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Ju","family":"An","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Ji","family":"Sung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hyung","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Pathology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-1999","authenticated-orcid":false,"given":"Young Shin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea."},{"name":"Department of Biomedical Science, Graduate School, CHA University, Seongnam, South Korea."},{"name":"Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010716-104908"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3028"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2020.01.002"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.05.047"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9111082"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgv122"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2010.06.006"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1957.02980130015004"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2019.101367"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.09.2459"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.09.3680"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00287"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.1963.sp001635"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.1982.tb02026.x"},{"issue":"2","key":"e_1_3_7_16_2","first-page":"149","article-title":"Experimental thyroiditis in the guinea pig. II. Electron microscopy","volume":"46","author":"Sobel HJ","year":"1965","unstructured":"Sobel HJ, , Geller J. Experimental thyroiditis in the guinea pig. II. Electron microscopy. Am J Pathol, 1965; 46(2):149\u2013163.","journal-title":"Am J Pathol"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.07.008"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00096"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2010-0253"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-014-0221-9"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpbi.5"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_3_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2012.05.008"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007857"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02656-4"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09663"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01197"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2017.02.020"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.269"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2011.05.003"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.179"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00278.2005"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.220211797"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa071834"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.093849"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.132826"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2019.06.012"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1532259"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1390539"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.2.7291"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1980"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12286"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3386"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.7"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.21"},{"key":"e_1_3_7_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0448-9"},{"key":"e_1_3_7_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00778"},{"key":"e_1_3_7_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11715"},{"key":"e_1_3_7_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00007.2009"},{"key":"e_1_3_7_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001914200"},{"key":"e_1_3_7_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.002"},{"key":"e_1_3_7_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.001"},{"key":"e_1_3_7_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.003"},{"key":"e_1_3_7_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2152"},{"key":"e_1_3_7_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2005.09.009"},{"key":"e_1_3_7_60_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.22.5.0444"},{"key":"e_1_3_7_61_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-61-6-1172"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2024.0125","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2024.0125","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2024.0125","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T07:27:25Z","timestamp":1775460445000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2024.0125"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":60,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1089\/thy.2024.0125"],"URL":"https:\/\/doi.org\/10.1089\/thy.2024.0125","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]}}}