Chronic Kidney Disease Induced by Cisplatin, Folic Acid and Renal Ischemia Reperfusion Induces Anemia and Promotes GATA-2 Activation in Mice

Autor(es)

Estrela, Gabriel Rufino ^{[1, 2]} ; Freitas-Lima, Leandro Ceotto ^[3] ; Budu, Alexandre ^[3] ; de Arruda, Adriano Cleis ^{[3, 2]} ; Perilhao, Mauro Sergio ^{[3, 2]} ; Fock, Ricardo Ambrosio ^[4] ; Barrera-Chimal, Jonatan ^{[5, 6]} ; Araujo, Ronaldo Carvalho ^{[3, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Clin & Expt Oncol, Hematol & Hematotherapy Discipline, BR-04037002 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Med, Nephrol Discipline, BR-04039032 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biophys, BR-04039032 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo - Brazil

^[5] Autonomous Univ Mexico, Inst Biomed Res, Ciudad Univ, Postal Mail 70228, Mexico City 04510, DF - Mexico

^[6] Natl Inst Cardiol Ignacio Chavez, Invest Unity UNAM INC, Mexico City 04360, DF - Mexico

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINES; v. 9, n. 7 JUL 2021.
• Citações Web of Science: 0

Resumo

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 HIF-2 alpha, erythropoietin, hepcidin, GATA-2, and GATA-2 target genes were also determined. All three CKD models presented increased levels of creatinine, urea, and proteinuria. Renal up-regulation of NGAL, KIM-1, and TNF-alpha mRNA levels was observed. Moreover, the three CKD models developed fibrosis and presented increased fibrotic markers and alpha-SMA protein levels. CKD induced decreased hemoglobin and ferritin levels and increased erythropoietin levels in the serum. Renal tissue showed decreased erythropoietin and HIF-2 alpha mRNA levels, while an increase in the iron metabolism regulator hepcidin was observed. GATA-2 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. (AU)

• Processo FAPESP: 17/23599-6 - Receptores de cininas e imunometabolismo
• Beneficiário: Leandro Ceotto Freitas Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/20082-7 - Sistema calicreína cininas no exercício físico e metabolismo
• Beneficiário: Ronaldo de Carvalho Araújo
• Modalidade de apoio: Auxílio à Pesquisa - Temático