Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment
Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RN...
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MDPI AG
2024-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/640 |
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| author | Kamyar Zahedi Sharon Barone Marybeth Brooks Tracy Murray Stewart Jackson R. Foley Ashley Nwafor Robert A. Casero Manoocher Soleimani |
| author_facet | Kamyar Zahedi Sharon Barone Marybeth Brooks Tracy Murray Stewart Jackson R. Foley Ashley Nwafor Robert A. Casero Manoocher Soleimani |
| author_sort | Kamyar Zahedi |
| collection | DOAJ |
| description | Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RNA-seq analyses revealed increases in the expression of markers of kidney injury (e.g., lipocalin 2 and kidney injury molecule 1) and fibrosis (e.g., collagen 1, fibronectin, and vimentin 1) in RLDC mice. In addition, we observed increased expression of polyamine catabolic enzymes (spermidine/spermine N<sup>1</sup>-acetyltransferase, <i>Sat1</i>, and spermine oxidase, <i>Smox</i>) and decreased expression of ornithine decarboxylase (<i>Odc1</i>), a rate-limiting enzyme in polyamine synthesis in mice subjected to RLDC. Upon confirmation of the RNA-seq results, we tested the hypothesis that enhanced polyamine catabolism contributes to the onset of renal injury and development of fibrosis. To test our hypothesis, we compared the severity of RLDC-induced renal injury and fibrosis in wildtype (WT), <i>Sat1</i>-KO, and <i>Smox</i>-KO mice. Our results suggest that the ablation of polyamine catabolic enzymes reduces the severity of renal injury and that modulation of the activity of these enzymes may protect against kidney damage and fibrosis caused by cisplatin treatment. |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:31:36Z |
| publishDate | 2024-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-c48f6db75b95420fbbfb46630f9bec282024-03-27T13:23:01ZengMDPI AGBiomedicines2227-90592024-03-0112364010.3390/biomedicines12030640Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin TreatmentKamyar Zahedi0Sharon Barone1Marybeth Brooks2Tracy Murray Stewart3Jackson R. Foley4Ashley Nwafor5Robert A. Casero6Manoocher Soleimani7Division of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADivision of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USADivision of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USAThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USAThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USAThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USAThe Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USADivision of Nephrology, Department of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USACisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RNA-seq analyses revealed increases in the expression of markers of kidney injury (e.g., lipocalin 2 and kidney injury molecule 1) and fibrosis (e.g., collagen 1, fibronectin, and vimentin 1) in RLDC mice. In addition, we observed increased expression of polyamine catabolic enzymes (spermidine/spermine N<sup>1</sup>-acetyltransferase, <i>Sat1</i>, and spermine oxidase, <i>Smox</i>) and decreased expression of ornithine decarboxylase (<i>Odc1</i>), a rate-limiting enzyme in polyamine synthesis in mice subjected to RLDC. Upon confirmation of the RNA-seq results, we tested the hypothesis that enhanced polyamine catabolism contributes to the onset of renal injury and development of fibrosis. To test our hypothesis, we compared the severity of RLDC-induced renal injury and fibrosis in wildtype (WT), <i>Sat1</i>-KO, and <i>Smox</i>-KO mice. Our results suggest that the ablation of polyamine catabolic enzymes reduces the severity of renal injury and that modulation of the activity of these enzymes may protect against kidney damage and fibrosis caused by cisplatin treatment.https://www.mdpi.com/2227-9059/12/3/640cisplatinnephrotoxicitychronic kidney injuryfibrosispolyaminepolyamine catabolism |
| spellingShingle | Kamyar Zahedi Sharon Barone Marybeth Brooks Tracy Murray Stewart Jackson R. Foley Ashley Nwafor Robert A. Casero Manoocher Soleimani Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment Biomedicines cisplatin nephrotoxicity chronic kidney injury fibrosis polyamine polyamine catabolism |
| title | Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment |
| title_full | Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment |
| title_fullStr | Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment |
| title_full_unstemmed | Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment |
| title_short | Polyamine Catabolism and Its Role in Renal Injury and Fibrosis in Mice Subjected to Repeated Low-Dose Cisplatin Treatment |
| title_sort | polyamine catabolism and its role in renal injury and fibrosis in mice subjected to repeated low dose cisplatin treatment |
| topic | cisplatin nephrotoxicity chronic kidney injury fibrosis polyamine polyamine catabolism |
| url | https://www.mdpi.com/2227-9059/12/3/640 |
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