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This study aimed to identify drugs that promote this repair phenotype, which is regulated by the expression of the transcription factor c\u2010Jun. Purmorphamine (PUR) and Smoothened agonist (SAG) are both Sonic Hedgehog (SHH) agonists that have been implicated in promoting regeneration after neurological injury in animal models. Here, we have demonstrated that SHH agonists significantly increased c\u2010Jun expression in rat primary SCs and promoted morphological and functional changes consistent with the repair SC phenotype, including an elongated bipolar morphology and increased secretion of neurotrophic factors. Notably, PUR consistently demonstrated a greater potency in driving these effects compared with SAG at the same concentrations. We also identified 2.5\u2009\u00b5M PUR as an effective dosage producing these measurable effects in vitro. Coculturing dorsal root ganglion (DRG) neurons with PUR\u2010treated SCs resulted in a marked increase in neurite elongation, suggesting that cell\u2010based or contact\u2010dependent features of repair SCs contribute to axon growth. These findings demonstrate that SHH agonists effectively reprogram SCs into a repair phenotype, which constitutes a potential therapeutic strategy for enhancing nerve regeneration and functional recovery in peripheral nerve injury treatment.<\/jats:p>","DOI":"10.1002\/bit.70049","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T06:26:26Z","timestamp":1755498386000},"page":"2967-2979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sonic Hedgehog Agonists Induce Repair Schwann Cells"],"prefix":"10.1002","volume":"122","author":[{"given":"Daniel","family":"Colchado","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Plastic and Reconstructive Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Department of Surgery, Division of General Surgery Washington University School of Medicine St. Louis Missouri 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