{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:03:01Z","timestamp":1790118181910,"version":"4.0.1"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Aristolochic acid A possesses anti-inflammatory, antispasmodic and diuretic pharmacological activities, while exerting strong toxic effects that cause irreversible renal tubular injury, renal fibrosis and malignant tumors such as urothelial carcinoma. This study aimed to elucidate the relationship between m6A methylation and AAA-induced nephrotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HK-2 cells were treated with AAA. Cell viability was detected to evaluate AAA-induced cytotoxicity. mRNA-seq and MeRIP-seq were performed to screen differentially expressed genes and identify m6A methylation profiles related to renal injury. Combined bioinformatics analysis and cellular validation experiments were used to explore the key regulatory factor and related pathological mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AAA significantly reduced the viability of HK-2 cells. mRNA-seq identified differentially expressed genes closely associated with oxidative stress and autophagy under AAA treatment. MeRIP-seq confirmed that m6A methylation alterations were tightly correlated with the expression of oxidative stress, autophagy and ferroptosis-related genes. IGF2BP2 was identified as a key mediator of AAA-induced cytotoxicity. Functional experiments further verified that AAA triggered oxidative stress, autophagy and ferroptosis in HK-2 cells, in which IGF2BP2 exerted a critical regulatory role.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that AAA-induced renal tubular cell damage is closely related to altered m6A methylation levels and dysregulated expression of m6A regulatory factors in target genes, revealing a novel epigenetic mechanism underlying AAA nephrotoxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1873549","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:11:31Z","timestamp":1790115091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated analysis of autophagy and ferroptosis mediating aristolochic acid A-induced nephrotoxicity via transcriptome and m6A epigenetic transcriptome in HK-2 cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Peichun","family":"Ye","sequence":"first","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Environment and Health, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Bao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongcheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lele","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Hu","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Environment and Health, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education","place":["Fuzhou, China"]},{"name":"Fujian Provincial Key Laboratory of Environment and Health, Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"20202","DOI":"10.1038\/s41598-025-06355-5","article-title":"Vincamine induces cytoprotective autophagy via regulation of ampk\/mtor signaling pathway in gentamicin-induced hepatotoxicity and nephrotoxicity in rats","volume":"15","author":"Abouelhamd","year":"2025","journal-title":"Sci. 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