Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice
Anemia is a common feature of chronic kidney disease (CKD). It is a process related to erythropoietin deficiency, shortened erythrocyte survival, uremic erythropoiesis inhibitors, and disordered iron homeostasis. Animal models of CKD-induced anemia are missing and would be desirable in order to stud...
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MDPI AG
2021-07-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/7/769 |
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| author | Gabriel Rufino Estrela Leandro Ceotto Freitas-Lima Alexandre Budu Adriano Cleis de Arruda Mauro Sergio Perilhão Ricardo Ambrósio Fock Jonatan Barrera-Chimal Ronaldo Carvalho Araújo |
| author_facet | Gabriel Rufino Estrela Leandro Ceotto Freitas-Lima Alexandre Budu Adriano Cleis de Arruda Mauro Sergio Perilhão Ricardo Ambrósio Fock Jonatan Barrera-Chimal Ronaldo Carvalho Araújo |
| author_sort | Gabriel Rufino Estrela |
| collection | DOAJ |
| description | Anemia is a common feature of chronic kidney disease (CKD). It is a process related to erythropoietin deficiency, shortened erythrocyte survival, uremic erythropoiesis inhibitors, and disordered iron homeostasis. Animal models of CKD-induced anemia are missing and would be desirable in order to study anemia mechanisms and facilitate the development of novel therapeutic tools. We induced three different models of CKD in mice and evaluated the development of anemia characteristics. Mice were subjected to unilateral ischemia-reperfusion or received repeated low doses of cisplatin or folic acid to induce nephropathy. Renal function, kidney injury and fibrotic markers were measured to confirm CKD. Moreover, serum hemoglobin, ferritin and erythropoietin were analyzed. Renal mRNA levels of <i>HIF-2α</i>, erythropoietin, hepcidin, <i>GATA-2</i>, and <i>GATA-2</i> target genes were also determined. All three CKD models presented increased levels of creatinine, urea, and proteinuria. Renal up-regulation of <i>NGAL</i>, <i>KIM-1</i>, and <i>TNF-α</i> mRNA levels was observed. Moreover, the three CKD models developed fibrosis and presented increased fibrotic markers and α-SMA protein levels. CKD induced decreased hemoglobin and ferritin levels and increased erythropoietin levels in the serum. Renal tissue showed decreased erythropoietin and <i>HIF-2α</i> mRNA levels, while an increase in the iron metabolism regulator hepcidin was observed. <i>GATA-2</i> transcription factor (erythropoietin repressor) mRNA levels were increased in all CKD models, as well as its target genes. We established three models of CKD-induced anemia, regardless of the mechanism and severity of kidney injury. |
| first_indexed | 2024-03-10T09:44:40Z |
| format | Article |
| id | doaj.art-0f5da22b70094abcb1ef1fb492d0ed82 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T09:44:40Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-0f5da22b70094abcb1ef1fb492d0ed822023-11-22T03:16:42ZengMDPI AGBiomedicines2227-90592021-07-019776910.3390/biomedicines9070769Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in MiceGabriel Rufino Estrela0Leandro Ceotto Freitas-Lima1Alexandre Budu2Adriano Cleis de Arruda3Mauro Sergio Perilhão4Ricardo Ambrósio Fock5Jonatan Barrera-Chimal6Ronaldo Carvalho Araújo7Department of Clinical and Experimental Oncology, Hematology and Hematotherapy Discipline, Federal University of São Paulo, São Paulo 04037-002, BrazilDepartment of Biophysics, Federal University of São Paulo, São Paulo 04039-032, BrazilDepartment of Biophysics, Federal University of São Paulo, São Paulo 04039-032, BrazilDepartment of Medicine, Nephrology Discipline, Federal University of São Paulo, São Paulo 04039-032, BrazilDepartment of Medicine, Nephrology Discipline, Federal University of São Paulo, São Paulo 04039-032, BrazilDepartment of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, University of Sâo Paulo, São Paulo 05508-000, BrazilInstitute of Biomedical Research, Autonomous University of Mexico, Ciudad Universitaria, Postal mail 70228, Mexico City 04510, MexicoDepartment of Medicine, Nephrology Discipline, Federal University of São Paulo, São Paulo 04039-032, BrazilAnemia is a common feature of chronic kidney disease (CKD). It is a process related to erythropoietin deficiency, shortened erythrocyte survival, uremic erythropoiesis inhibitors, and disordered iron homeostasis. Animal models of CKD-induced anemia are missing and would be desirable in order to study anemia mechanisms and facilitate the development of novel therapeutic tools. We induced three different models of CKD in mice and evaluated the development of anemia characteristics. Mice were subjected to unilateral ischemia-reperfusion or received repeated low doses of cisplatin or folic acid to induce nephropathy. Renal function, kidney injury and fibrotic markers were measured to confirm CKD. Moreover, serum hemoglobin, ferritin and erythropoietin were analyzed. Renal mRNA levels of <i>HIF-2α</i>, erythropoietin, hepcidin, <i>GATA-2</i>, and <i>GATA-2</i> target genes were also determined. All three CKD models presented increased levels of creatinine, urea, and proteinuria. Renal up-regulation of <i>NGAL</i>, <i>KIM-1</i>, and <i>TNF-α</i> mRNA levels was observed. Moreover, the three CKD models developed fibrosis and presented increased fibrotic markers and α-SMA protein levels. CKD induced decreased hemoglobin and ferritin levels and increased erythropoietin levels in the serum. Renal tissue showed decreased erythropoietin and <i>HIF-2α</i> mRNA levels, while an increase in the iron metabolism regulator hepcidin was observed. <i>GATA-2</i> transcription factor (erythropoietin repressor) mRNA levels were increased in all CKD models, as well as its target genes. We established three models of CKD-induced anemia, regardless of the mechanism and severity of kidney injury.https://www.mdpi.com/2227-9059/9/7/769chronic kidney diseaseanemiaexperimental disease model |
| spellingShingle | Gabriel Rufino Estrela Leandro Ceotto Freitas-Lima Alexandre Budu Adriano Cleis de Arruda Mauro Sergio Perilhão Ricardo Ambrósio Fock Jonatan Barrera-Chimal Ronaldo Carvalho Araújo Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice Biomedicines chronic kidney disease anemia experimental disease model |
| title | Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice |
| title_full | Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice |
| title_fullStr | Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice |
| title_full_unstemmed | Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice |
| title_short | Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice |
| title_sort | chronic kidney disease induced by cisplatin folic acid and renal ischemia reperfusion induces anemia and promotes gata 2 activation in mice |
| topic | chronic kidney disease anemia experimental disease model |
| url | https://www.mdpi.com/2227-9059/9/7/769 |
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