| Texto completo | |
| Autor(es): |
Costa-Pessoa, Juliana Martins
;
de Ponte, Mariana Charleaux
;
Braz, Heitor Macedo
;
Cruz, Mario Costa
;
Lopes-Goncalves, Guilherme
;
Oliveira-Souza, Maria
Número total de Autores: 6
|
| Tipo de documento: | Artigo Científico |
| Fonte: | AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 329, n. 2, p. 15-pg., 2025-08-04. |
| Resumo | |
Acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) contributes to a high rate of morbidity and mortality in many clinical settings. We hypothesized that I/R-induced proximal tubule (PT) injury is associated with inflammation and apoptosis and that PT cell injury may impair Na+/H+ exchanger isoform 3 (NHE3) activity. This study aimed to investigate the relationship between PT injury and NHE3 activity, analyzing the contribution of the p38MAPK/ezrin signaling pathway. To this end, we used in vivo and in vitro models of I/R. For the in vivo approach, 8-wk-old C57BL/6J mice were subjected to bilateral kidney I/R and compared with the sham-treated group. In vitro, TKPTS cells (mouse proximal tubular cell line) were subjected to I/R by treatment with antimycin A (5 mu M) and/or SB203580 (1 mu M; p38MAPK inhibitor) or NSC305787 (3.2 mu M; ezrin phosphorylation inhibitor) and compared with respective controls. Renal I/R in mice resulted in PT injury, severe inflammation, increased p38MAPK activation, reduced phospho (p-)ezrin immunostaining, and decreased colocalization of NHE3 with both villin and p-ezrin. Similarly, in vitro I/R caused cell apoptosis, increased p38MAPK activation, induced translocation of ezrin from the membrane to the cytosol, and reduced NHE3 activity. Thus, these findings suggest that in ischemic AKI tubulointerstitial injury is driven by inflammation and apoptosis, mediated through p38MAPK activation and altered ezrin function, ultimately impairing NHE3 activity and exacerbating cell injury. (AU) | |
| Processo FAPESP: | 22/01288-7 - Fatores envolvidos na progressão da lesão renal induzida por nefropatia cristalina ou isquemia/reperfusão: estudos in vivo e in vitro |
| Beneficiário: | Maria Oliveira de Souza |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 24/00266-5 - Participação da via de sinalização MAPK e do fator de transcrição Egr-1 na glomeruloesclerose |
| Beneficiário: | Heitor Macedo Braz |
| Modalidade de apoio: | Bolsas no Brasil - Mestrado |
| Processo FAPESP: | 16/12354-0 - Análise da transição da lesão renal aguda pós-isquêmica para a doença renal crônica e a contribuição da diabetes mellitus neste processo |
| Beneficiário: | Mariana Charleaux de Ponte |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 22/05371-6 - Implicações da sinalização apelinérgica sobre o transporte renal de sódio e água: papel da isquemia/reperfusão |
| Beneficiário: | Guilherme Lopes Gonçalves |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 24/22770-7 - Papel das metaloproteinases de matriz no desenvolvimento e progressão da fibrose renal. |
| Beneficiário: | Maria Oliveira de Souza |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |