{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:04:07Z","timestamp":1789592647046,"version":"build-2803163510"},"reference-count":65,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"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":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      We previously demonstrated that aryl hydrocarbon receptor (AhR) activation attenuates the cytoprotective effect of hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S), leading to indoxyl sulfate (IS)-mediated renal tubular damage. However, it is unclear whether this pathway would be present in an\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      uremic model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In a rat chronic kidney disease (CKD) model with 5\/6 nephrectomized (Nx), we found that poor renal filtration is associated with accumulation of IS and homocysteine (Hcy), an H\n                      <jats:sub>2<\/jats:sub>\n                      S precursor. Compared with controls, the protein and mRNA levels of H\n                      <jats:sub>2<\/jats:sub>\n                      S-producing enzymes, including cystathionine \u03b2-synthase, cystathionine \u03b3-lyase, and 3-mercaptopyruvate sulfurtransferase, were attenuated in Nx kidneys. Since the transcription factor, specificity protein 1 (Sp1), acts as an upstream regulator of these enzyme expressions, we found that the protein level and activity of Sp1 were significantly decreased in Nx kidneys. Interestingly, employing the blocker of the AhR CH-223191 not only reverses the decrease in H\n                      <jats:sub>2<\/jats:sub>\n                      S-producing enzymes and Sp1, but it also reverses H\n                      <jats:sub>2<\/jats:sub>\n                      S reduction in Nx rats. These are associated with the mitigation of plasma Hcy accumulation, renal excretion, perfusion insufficiency, and tubular damage. Moreover, the oxidative stress in Nx kidneys due to increased superoxide formation and decreased glutathione contents was also attenuated by AhR inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>\n                      Our findings highlight the deleterious effect of AhR activation on renal H\n                      <jats:sub>2<\/jats:sub>\n                      S formation may be due to IS accumulation and underline AhR blockade as a novel therapy for CKD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      AhR is detrimental to Sp1 function\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      , leading to impeding renal H\n                      <jats:sub>2<\/jats:sub>\n                      S generation and exacerbating oxidative stress during CKD progression.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      43, 448\u2013464.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2024.0833","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T08:09:56Z","timestamp":1751875796000},"page":"448-464","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Blockade of Aryl Hydrocarbon Receptor Ameliorates Functional Insufficiency in 5\/6 Nephrectomized Rat Kidneys by Restoring Hydrogen Sulfide Formation"],"prefix":"10.1177","volume":"43","author":[{"given":"Chien-Lin","family":"Lu","sequence":"first","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan."},{"name":"Division of Nephrology, Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Shiou","family":"Tseng","sequence":"additional","affiliation":[{"name":"Division of Urology, Department of Surgery, Far Eastern Memorial Hospital, New Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Bin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Hou","family":"Liao","sequence":"additional","affiliation":[{"name":"Divisions of Urology, Department of Surgery, Cardinal Tien Hospital, New Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0040-5203","authenticated-orcid":false,"given":"Ming-Chieh","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_3_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr560"},{"key":"e_1_3_6_3_1","doi-asserted-by":"publisher","DOI":"10.1717\/9\/excli2017-711"},{"key":"e_1_3_6_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2008121269"},{"key":"e_1_3_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-007-0011-8"},{"key":"e_1_3_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00354.x"},{"key":"e_1_3_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.11.010"},{"key":"e_1_3_6_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/0886022x.2022.2107936"},{"key":"e_1_3_6_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115634109"},{"key":"e_1_3_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0167-4781(02)00509-2"},{"key":"e_1_3_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104930200"},{"key":"e_1_3_6_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23126719"},{"key":"e_1_3_6_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5478708"},{"key":"e_1_3_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv226"},{"key":"e_1_3_6_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108448"},{"key":"e_1_3_6_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207698"},{"key":"e_1_3_6_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2282"},{"key":"e_1_3_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.21.12310"},{"key":"e_1_3_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2015.01.005"},{"key":"e_1_3_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105772"},{"key":"e_1_3_6_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00462.2014"},{"key":"e_1_3_6_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41100-018-0195-2"},{"key":"e_1_3_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2023.106788"},{"key":"e_1_3_6_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000444900"},{"key":"e_1_3_6_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176212"},{"key":"e_1_3_6_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11020361"},{"key":"e_1_3_6_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126204"},{"key":"e_1_3_6_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060936"},{"key":"e_1_3_6_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310211200"},{"key":"e_1_3_6_30_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00144.x"},{"key":"e_1_3_6_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.407833"},{"key":"e_1_3_6_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043518"},{"key":"e_1_3_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15062"},{"key":"e_1_3_6_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03776-9"},{"key":"e_1_3_6_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14020100"},{"key":"e_1_3_6_36_1","doi-asserted-by":"publisher","DOI":"10.1159\/000092198"},{"key":"e_1_3_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp378"},{"key":"e_1_3_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.285"},{"key":"e_1_3_6_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.23-09-03597.2003"},{"key":"e_1_3_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2021.09.012"},{"key":"e_1_3_6_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10030373"},{"key":"e_1_3_6_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi901786x"},{"key":"e_1_3_6_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-010-9079-y"},{"key":"e_1_3_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.449"},{"key":"e_1_3_6_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-16-0069"},{"key":"e_1_3_6_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00461.2020"},{"key":"e_1_3_6_47_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs20200973"},{"key":"e_1_3_6_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1744-9987.2007.00430.x"},{"key":"e_1_3_6_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.2005.01415.x"},{"key":"e_1_3_6_50_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9100925"},{"key":"e_1_3_6_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-019-1238-9"},{"key":"e_1_3_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.09.002"},{"key":"e_1_3_6_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02617.x"},{"key":"e_1_3_6_54_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.0550031028.x"},{"key":"e_1_3_6_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.132142"},{"key":"e_1_3_6_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202402066"},{"key":"e_1_3_6_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00096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