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We previously identified a peptide derived from human fibroblast growth factor 7 (FGF7p) that blocks urothelial apoptosis similar to full‐length FGF7, although effects of FGF7p on urothelial repair are unknown. Also, while urothelial AKT activation downstream of FGF7p correlated with the anti‐apoptotic effects, we have not directly interrogated the role of AKT in mediating the cytoprotection. Our goal was to assess effects of FGF7p on urothelial repair and the role of AKT signaling in mediating the cytoprotective effects of FGF7p. We performed hematoxylin and eosin (H&E), TUNEL, and/or immunofluorescence (IF) staining for various markers in FGF7p‐treated mice 28 days after giving cyclophosphamide or after co‐administering a systemic AKT antagonist with FGF7p 24 h after cyclophosphamide. Vehicle‐treated and injured mice had hyperplastic urothelium, incomplete return of mature superficial cell markers, ongoing proliferation, and continued presence of basal progenitor markers 28 days after injury; conversely, FGF7p‐treated mice had normal numbers of urothelial cell layers, nearly complete return of superficial cell markers, limited proliferation and fewer basal progenitor cells 28 days post‐injury. Vehicle‐treated mice also had ectopic lumenal basal progenitor cell markers, while FGF7p had none 28 days after cyclophosphamide. Co‐administration of an AKT inhibitor largely abrogated FGF7p‐driven AKT activation and cytoprotection in urothelium 24 h after injury. Thus, FGF7p drives faster and higher fidelity urothelial repair by limiting apoptotic injury via AKT signaling, similar to full‐length FGF7. Finally, FGF7p is much less expensive to synthesize and has a longer shelf life and higher purity than FGF7. [ABSTRACT FROM AUTHOR]

Although full‐length fibroblast growth factor 7 (FGF7) blocks cyclophosphamide‐induced urothelial apoptosis in mice, limitations include high production costs because of its large size. We previously identified a small peptide derived from FGF2 that mitigated acute radiation syndrome as well as full‐length FGF2. Based on the sequence of the FGF2 peptide, we synthesized a corresponding 19 amino acid FGF7 peptide (FGF7p). Our objectives were to determine if systemic FGF7p triggered the downstream targets and protected against cyclophosphamide bladder injury similar to full‐length FGF7. We administered FGF7p or vehicle subcutaneously (SQ) to mice subjected to no injury or intraperitoneal (IP) cyclophosphamide and harvested bladders 1 day after injury. We then performed hematoxylin and eosin, TUNEL and immunofluorescence (IF) staining. In uninjured mice, a 20 mg/kg threshold FGF7p dose induced expression of phosphorylated (activated) FRS2α (pFRS2α), and pAKT in urothelium (consistent with cytoprotective effects of FGF7). We then gave FGF7p (20 mg/kg) or vehicle at 72 and 48 h prior to cyclophosphamide. One day after injury, TUNEL staining revealed many more apoptotic urothelial cells with vehicle treatment versus FGF7p treatment. IF for pAKT and readouts of two anti‐apoptotic AKT targets (BAD and mTORC1) revealed minimal staining with vehicle treatment, but strong urothelial expression for all markers with FGF7p treatment. In conclusion, FGF7p appears to block bladder urothelial apoptosis via AKT and its targets, similar to FGF7. FGF7p is much more inexpensive to make and has a longer shelf life and higher purity than FGF7. [ABSTRACT FROM AUTHOR]