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FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988121/ https://www.ncbi.nlm.nih.gov/pubmed/35388988 http://dx.doi.org/10.14814/phy2.15241 |
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author | Narla, Sridhar Tatarao Rice, Lori Ostrov, David Swarts, Steven G. Siemann, Dietmar W. Bushnell, Daniel Scott Holden, Jacqueline G. Duara, Joanne Lindsey Bates, Carlton Matthew |
author_facet | Narla, Sridhar Tatarao Rice, Lori Ostrov, David Swarts, Steven G. Siemann, Dietmar W. Bushnell, Daniel Scott Holden, Jacqueline G. Duara, Joanne Lindsey Bates, Carlton Matthew |
author_sort | Narla, Sridhar Tatarao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8988121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89881212022-04-11 FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide Narla, Sridhar Tatarao Rice, Lori Ostrov, David Swarts, Steven G. Siemann, Dietmar W. Bushnell, Daniel Scott Holden, Jacqueline G. Duara, Joanne Lindsey Bates, Carlton Matthew Physiol Rep Original Articles 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. John Wiley and Sons Inc. 2022-04-07 /pmc/articles/PMC8988121/ /pubmed/35388988 http://dx.doi.org/10.14814/phy2.15241 Text en © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Narla, Sridhar Tatarao Rice, Lori Ostrov, David Swarts, Steven G. Siemann, Dietmar W. Bushnell, Daniel Scott Holden, Jacqueline G. Duara, Joanne Lindsey Bates, Carlton Matthew FGF7 peptide (FGF7p) mimetic mitigates bladder urothelial injury from cyclophosphamide |
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 | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988121/ https://www.ncbi.nlm.nih.gov/pubmed/35388988 http://dx.doi.org/10.14814/phy2.15241 |
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