Therapeutic Potential of Compounds with High Affinity to BAG2 in Inhibiting Keloid Disease.

PURPOSE: Targeting the distinct genetic and protein expression profiles of keloids necessitates the identification of novel therapeutic targets. This study was aimed to elucidate the role of Bcl-2-associated athanogene 2 (BAG2) in keloid pathology and identify compounds with high-affinity to BAG2. PATIENTS AND METHODS: Cell migration, and cell proliferation assays, along with flow cytometry, were used to evaluate the effects of BAG2 on keloid fibroblasts (KFs) derived from tissue samples of patients with abdominal or chest keloids. Additionally, histological examinations and Western blotting were performed to investigate BAG2's role in keloids. Surface plasmon resonance (SPR) was employed to identify compounds with high-affinity to BAG2, and the effects of these compounds on keloids was assessed. RESULTS: Inhibition of BAG2 significantly decreased collagen deposition, cell proliferation and migration in keloid tissues. The modulatory effect of BAG2 on these processes appears to be mediated partly by the MEK signaling pathway. Among the tested compounds, Bazedoxifene acetate and Ponesimod showed high affinity for BAG2 and demonstrated a more pronounced inhibitory effect on collagen deposition of the keloid tissues than other candidates. CONCLUSION: This study revealed the pathogenic role of BAG2 in keloid and identified compounds with high-affinity to BAG2, Bazedoxifene acetate and Ponesimod. The therapeutic capabilities of these compounds demonstrated their potential to improve therapeutic strategies for localized, targeted treatment to keloids.