{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:56:09Z","timestamp":1787676969513,"version":"build-2784847793"},"reference-count":61,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["UMO-2018\/30\/E\/NZ5\/00458"],"award-info":[{"award-number":["UMO-2018\/30\/E\/NZ5\/00458"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY033391"],"award-info":[{"award-number":["R01EY033391"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY033141"],"award-info":[{"award-number":["R01EY033141"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Minister of Science"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic peripheral neuropathy (DPN) is a serious consequence of prolonged hyperglycemia and contributes to the morbidity associated with diabetes. Hyperglycemia enhances the non-enzymic glycation of proteins and the accumulation of Advanced Glycation End Products (AGEs). We employed a diabetic mouse model lacking both Diaph1 and RAGE to elucidate the role of RAGE-Diaph1 signaling in the pathogenesis of DPN. We demonstrate that simultaneous deletion of Diaph1 and RAGE did not change the course or the intensity of hyperglycemia-induced weight loss in mice. However, abrogating RAGE-Diaph1 signaling affects actin cytoskeleton remodeling rates in nerve axons by altering the ratio of the actin-regulating molecules cofilin and profilin. Our experimental results suggest that the loss of RAGE-Diaph1 signaling protects neurons from hyperglycemic conditions. We observed a beneficial effect of abolishing RAGE-Diaph1 signaling on the axonal structure of neuropathic nerves. In addition, we observed that abolishing RAGE-Diaph1 signaling improved motor nerve conduction velocity in the sciatic nerves of hyperglycemic mice. Our data indicate that RAGE-Diaph1 signaling is likely enhanced in chronic hyperglycemia, resulting in aberrant actin dynamics in nerve axons. These defective actin dynamics play a key role in the progression of DPN, leading to structural and functional loss in peripheral nerves.<\/jats:p>","DOI":"10.3390\/ijms262211182","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T15:03:15Z","timestamp":1763564595000},"page":"11182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Effect of RAGE-Diaph1 Signaling Inhibition on the Progression of Peripheral Neuropathy in Diabetic Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6577-7545","authenticated-orcid":false,"given":"Kamila","family":"Zglejc-Waszak","sequence":"first","affiliation":[{"name":"Department of Anatomy and Histology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-085 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Korytko","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-085 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-5790","authenticated-orcid":false,"given":"Bernard","family":"Kordas","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-085 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Pomianowski","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2604-926X","authenticated-orcid":false,"given":"Bogdan","family":"Lewczuk","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0856-3644","authenticated-orcid":false,"given":"Joanna","family":"Wojtkiewicz","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-085 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"W\u0105sowicz","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabella","family":"Babi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Forensic Veterinary Medicine and Administration, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6922-9554","authenticated-orcid":false,"given":"Konark","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judyta Karolina","family":"Juranek","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-085 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1007\/s12264-022-00878-x","article-title":"Role of RAGE in the Pathogenesis of Neurological Disorders","volume":"38","author":"Juranek","year":"2022","journal-title":"Neurosci. 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