FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide
Abstract 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 wel...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-04-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15241 |
| _version_ | 1797387902671388672 |
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| author | Sridhar Tatarao Narla Lori Rice David Ostrov Steven G. Swarts Dietmar W. Siemann Daniel Scott Bushnell Jacqueline G. Holden Joanne Lindsey Duara Carlton Matthew Bates |
| author_facet | Sridhar Tatarao Narla Lori Rice David Ostrov Steven G. Swarts Dietmar W. Siemann Daniel Scott Bushnell Jacqueline G. Holden Joanne Lindsey Duara Carlton Matthew Bates |
| author_sort | Sridhar Tatarao Narla |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-08T22:32:56Z |
| format | Article |
| id | doaj.art-f41c6f06f6174b17a3bb9dd533a81ed8 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-08T22:32:56Z |
| publishDate | 2022-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-f41c6f06f6174b17a3bb9dd533a81ed82023-12-18T02:20:40ZengWileyPhysiological Reports2051-817X2022-04-01107n/an/a10.14814/phy2.15241FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamideSridhar Tatarao Narla0Lori Rice1David Ostrov2Steven G. Swarts3Dietmar W. Siemann4Daniel Scott Bushnell5Jacqueline G. Holden6Joanne Lindsey Duara7Carlton Matthew Bates8Division of Nephrology Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USADepartment of Radiation Oncology College of Medicine University of Florida Gainesville Florida USADepartment of Pathology, Immunology and Laboratory Medicine University of Florida College of Medicine Gainesville Florida USADepartment of Radiation Oncology College of Medicine University of Florida Gainesville Florida USADepartment of Radiation Oncology College of Medicine University of Florida Gainesville Florida USADivision of Nephrology Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USADivision of Nephrology Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USADivision of Neonatology Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USADivision of Nephrology Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USAAbstract 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.https://doi.org/10.14814/phy2.15241bladdercyclophosphamideFGF7pfibroblast growth factor 7 peptideurothelium |
| spellingShingle | Sridhar Tatarao Narla Lori Rice David Ostrov Steven G. Swarts Dietmar W. Siemann Daniel Scott Bushnell Jacqueline G. Holden Joanne Lindsey Duara Carlton Matthew Bates FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide Physiological Reports bladder cyclophosphamide FGF7p fibroblast growth factor 7 peptide urothelium |
| title | FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide |
| title_full | FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide |
| title_fullStr | FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide |
| title_full_unstemmed | FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide |
| title_short | FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide |
| title_sort | fgf7 peptide fgf7p mimetic mitigates bladder urothelial injury from cyclophosphamide |
| topic | bladder cyclophosphamide FGF7p fibroblast growth factor 7 peptide urothelium |
| url | https://doi.org/10.14814/phy2.15241 |
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