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IGF2BP2 is a single\u2010stranded RNA\u2010binding protein that has recently been identified as an m6A reader; however, its role and regulatory effects in Schwann cells during DPN remain largely unknown. In this study, we demonstrated that high\u2010glucose exposure significantly increased IGF2BP2 levels in RSC96 cells and in the sciatic nerves of both type 1 and type 2 diabetic mice, accompanied by reduced autophagy and neurotrophin expression. Consistently, IGF2BP2 expression was associated with metabolic and immune\u2010related parameters in patients with type 2 diabetes. Functionally, IGF2BP2 overexpression inhibited, whereas its downregulation partially rescued, high glucose\u2013induced suppression of autophagy and neurotrophin expression in\u00a0vitro (RSC96 cells) and in\u00a0vivo (\n                    <jats:italic>IGF2BP2<\/jats:italic>\n                    knockout mice). Mechanistically, IGF2BP2 bound to EGR1 mRNA in an m6A modification\u2010dependent manner, primarily recognizing an adenosine at position 1268, thereby enhancing EGR1 mRNA stability. Downregulation of EGR1 alleviated the inhibitory effects of IGF2BP2 overexpression on autophagy and neurotrophin expression in RSC96 cells. Conversely, EGR1 overexpression attenuated the protective effects of\n                    <jats:italic>IGF2BP2<\/jats:italic>\n                    knockout on peripheral nerve function and neurotrophic signaling in diabetic mice. Overall, high\u2010glucose stimulation upregulated IGF2BP2, which enhanced EGR1 mRNA stability in an m6A\u2010dependent manner, thereby suppressing autophagy and neurotrophin expression in Schwann cells during DPN.\n                  <\/jats:p>","DOI":"10.1096\/fj.202600579r","type":"journal-article","created":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:40:26Z","timestamp":1778924426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>m6A<\/scp>\n                    Reader\n                    <scp>IGF2BP2<\/scp>\n                    Regulates Schwann Cell Autophagy and Neurotrophin Expression via\n                    <scp>EGR1<\/scp>\n                    in Diabetic Peripheral Neuropathy"],"prefix":"10.1096","volume":"40","author":[{"given":"Wandi","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pathology Hebei Medical University  Shijiazhuang 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