{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:49:14Z","timestamp":1791438554604,"version":"4.3.3"},"reference-count":71,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271648"],"award-info":[{"award-number":["82271648"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101693"],"award-info":[{"award-number":["82101693"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetes mellitus\u2010induced erectile dysfunction (DMED) is a common and debilitating vascular\u2010neurogenic complication of diabetes. The poor responsiveness of DMED patients to phosphodiesterase type\u20105 inhibitors underscores the need for therapies capable of restoring both endothelial integrity and cavernous nerve function. The Slit2\/Roundabout (Robo) pathway, a conserved regulator of axon guidance and vascular remodeling, is well positioned to coordinate neurovascular repair; however, its involvement in DMED remains largely undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single\u2010cell RNA sequencing from embryonic genital tubercle to postnatal stages was used to map fibroblast\u2010endothelial\u2010neuronal signaling and identify Slit2 as a key secreted ligand. Diabetic and control mouse corpus cavernosum tissues were analyzed for endothelial and neuronal Slit2\u2010Robo1\/4 activity. In vitro, recombinant Slit2\u2010N was applied to cells under high glucose to assess proliferation, migration, tube\/sprout formation, and neurite outgrowth; Robo1\/4 knockdown tested receptor dependency. In vivo, AAV\u2010Slit2 was delivered intracavernously to diabetic mice, with erectile function assessed by sodium\u2010nitroprusside perfusion and electrostimulation, and structural remodeling evaluated by endothelial, neural, and fibrosis markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Single\u2010cell profiling identified Slit2 as a fibroblast\u2010derived developmental cue for corpus cavernosum morphogenesis. Diabetic mice exhibited markedly reduced endothelial and neuronal Slit2\u2010Robo signaling. Slit2\u2010N restored angiogenic and neuroregenerative functions in vitro under high glucose, enhancing endothelial activity and neurite growth; all effects were lost after Robo1\/4 silencing. In vivo, AAV\u2010Slit2 re\u2010established local Slit2 signaling, improved penile perfusion and erectile responses, enhanced endothelial proliferation and nerve regeneration, and reduced fibrosis, indicating substantial neurovascular recovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Slit2\/Robo signaling is a key regulatory axis disrupted in DMED. Local restoration of Slit2 via AAV delivery drives synchronized neurovascular regeneration and effectively rescues erectile function in diabetic mice. These findings establish Slit2 as a promising therapeutic target for reversing the underlying pathophysiology of DMED rather than merely providing symptomatic relief.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70288","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:46:12Z","timestamp":1781779572000},"page":"1831-1846","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Slit2\/Robo Signaling Restores Diabetic Erectile Function via Neurovascular Remodeling"],"prefix":"10.1111","volume":"14","author":[{"given":"Sen","family":"Fu","sequence":"first","affiliation":[{"name":"Department and Institute of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 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