{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:20:45Z","timestamp":1792167645786,"version":"4.4.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"2024 China National Health Commission Research Project","award":["WKZX2024ED1018"],"award-info":[{"award-number":["WKZX2024ED1018"]}]},{"name":"2025 Research Projects of Sichuan Medical Association","award":["S20250084"],"award-info":[{"award-number":["S20250084"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erectile dysfunction (ED) is a prevalent complication of type 2 diabetes mellitus (T2DM). However, the role of RNA N6-methyladenosine (m6A) methylation in T2DM-associated ED remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To determine whether m6A demethylation of TNFAIP3-interacting protein 1 (TNIP1) RNA mediated by fat mass and obesity-associated protein (FTO) regulates pyroptosis in corpus cavernosum endothelial cells in T2DM and contributes to ED.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The endothelial cells of the penile corpus cavernosum were obtained from Sprague\u2013Dawley (SD) rats aged 8\u00a0weeks and assigned to five groups as follows: Control group, KD-FTO group that treated with the FTO-targeting siRNA lentivirus, OE-FTO group that treated with the FTO-overexpression lentiviral vector, KD-NC group that treated with the control siRNA lentivirus, and OE-NC group that treated with the empty FTO-overexpression lentiviral vector. The levels of FTO, TNIP1, NF\u03baB, caspase-1, p-eNOS\/eNOS, and NO were measured. TNIP1 mRNA stability was assessed. Male SD rats aged 8\u00a0weeks were randomly allocated to six groups: Control group, NC\u2009+\u2009Con group that SD rats treated with the empty lentivirus, NC\u2009+\u2009FTO-OE group that SD rats treated with the lentiviral vector carrying an over-expressed FTO gene, T2DM rats, T2DM\u2009+\u2009Con group that T2DM rats treated with the empty lentivirus, and T2DM\u2009+\u2009FTO-KD group that T2DM rats treated with the lentivirus carrying an siRNA targeting FTO. Two weeks after injection, the expression of FTO, TNIP1, caspase-1, p-eNOS\/eNOS, as well as the ratio of pyroptotic endothelial cells in the penile corpus cavernosum, was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>Upregulation of FTO in the penile corpus cavernosum of T2DM rats promoted m6A demethylation of TNIP1 mRNA, decreased TNIP1 expression, and enhanced the NF\u03baB\/caspase-1 pathway, thereby increasing endothelial pyroptosis and reducing ED.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the NC group, the T2DM group exhibited significantly increased FTO expression, whereas global RNA m6A methylation, ICPmax\/MAP, p-eNOS\/eNOS, and NO levels were significantly decreased (P\u00a0&amp;lt;\u2009.05). Compared with the T2DM group, the T2DM\u2009+\u2009FTO-KD group showed markedly higher TNIP1 levels, p-eNOS\/eNOS, and ICPmax\/MAP, accompanied by reduced expression of FTO, NF\u03baB, caspase-1, and significantly lower pyroptotic endothelial cells (P\u00a0&amp;lt;\u2009.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical implications<\/jats:title>\n                    <jats:p>Targeting FTO-mediated TNIP1 m6A demethylation may offer a therapeutic strategy for T2DM-associated ED.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Strengths and limitations<\/jats:title>\n                    <jats:p>Other m6A regulators potentially involved in this process were not assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In T2DM, upregulated FTO promoted m6A demethylation of TNIP1 mRNA, downregulated TNIP1 expression, enhanced NF\u03baB\/caspase-1 signaling, and increased endothelial cell pyroptosis in the penile corpus cavernosum, thereby contributing to ED.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdag119","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T11:22:10Z","timestamp":1775474530000},"source":"Crossref","is-referenced-by-count":2,"title":["Upregulated FTO promotes TNIP1 m6A demethylation induced penile corpus cavernosum endothelial pyroptosis and erectile dysfunction in type 2 diabetic rats"],"prefix":"10.1093","volume":"23","author":[{"given":"Chunyang","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Urology, The Affiliated Hospital of Southwest Medical University , Luzhou, Sichuan 646000 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