{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:40:49Z","timestamp":1777887649282,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82305219\u300182474480\u548c82204917"],"award-info":[{"award-number":["82305219\u300182474480\u548c82204917"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) is a major global health burden with substantial morbidity and mortality. Proteinuria is strongly associated with adverse renal outcomes, and podocyte pyroptosis is increasingly recognized as a key driver of glomerular filtration barrier disruption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study sought to elucidate how Modified Huangqi Chifeng Decoction (MHCD) mitigates renal and podocyte injury by modulating the Arid5a\/AIM2-dependent pyroptosis pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      An adriamycin-induced nephropathy (ADR) rat model and an\n                      <jats:italic>in vitro<\/jats:italic>\n                      podocyte injury model were established. Twenty-four-hour urinary protein levels, serum biochemical indices, and renal histopathology were assessed. Expression of Arid5a, AIM2, and downstream pyroptosis-related molecules (Caspase-1, ASC oligomerization, GSDMD, IL-1\u03b2, and IL-18) was quantified. Mutagenesis of Arid5a binding sites in the AIM2 promoter, along with electrophoretic mobility shift assays (EMSA) and dual-luciferase reporter assays, were used to validate Arid5a\u2019s promoter binding and its transcriptional regulation of AIM2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MHCD markedly reduced proteinuria, alleviated renal histopathological damage, and improved podocyte viability in ADR rats. These protective effects coincided with downregulation of Arid5a, AIM2, and downstream pyroptosis mediators\u2014including Caspase-1, ASC oligomers, GSDMD, IL-1\u03b2, and IL-18. Mechanistically, Arid5a functioned as a transcription factor that binds to the AIM2 promoter to regulate AIM2 expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MHCD mitigates renal and podocyte injury by suppressing inflammasome activation and pyroptosis through Arid5a-mediated transcriptional activation of the AIM2 signaling axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1822567","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:19:53Z","timestamp":1777609193000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the mechanism by which modified huangqi chifeng decoction protects podocytes via Arid5a-mediated transcriptional regulation of the AIM2 pyroptosis signaling 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