Chronic exposure to hypoxia attenuates renal injury and innate immunity activation in the remnant kidney model

Autor(es):Mostrar menos -

Tono Rempel, Lisienny Campoli ^[1] ; Faustino, Viviane Dias ^[1] ; Foresto-Neto, Orestes ^[1] ; Fanelli, Camilla ^[1] ; Alarcon Arias, Simone Costa ^[1] ; da Silva Moreira, Gizely Cristina ^[1] ; Nascimento, Thalita Fabiana ^[1] ; Avila, Victor Ferreira ^[1] ; Costa Malheiros, Denise Maria Avancini ^[1] ; Saraiva Camara, Niels Olsen ^{[1, 2]} ; Fujihara, Clarice Kazue ^[1] ; Zatz, Roberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Clin Med, Renal Div, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Lab Transplantat Immunobiol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 317, n. 5, p. F1285-F1292, NOV 2019.
• Citações Web of Science: 0

Resumo

Hypoxia is thought to influence the pathogenesis of chronic kidney disease, but direct evidence that prolonged exposure to tissue hypoxia initiates or aggravates chronic kidney disease is lacking. We tested this hypothesis by chronically exposing normal rats and rats with 5/6 nephrectomy (Nx) to hypoxia. In addition, we investigated whether such effect of hypoxia would involve activation of innate immunity. Adult male Munich-Wistar rats underwent Nx (n = 54) or sham surgery (sham; n = 52). Twenty-six sham rats and 26 Nx rats remained in normoxia, whereas 26 sham rats and 28 Nx rats were kept in a normobaric hypoxia chamber (12% O-2) for 8 wk. Hypoxia was confirmed by immunohistochemistry for pimonidazole. Hypoxia was confined to the medullary area in sham + normoxia rats and spread to the cortical area in sham + hypoxia rats, without changing the peritubular capillary density. Exposure to hypoxia promoted no renal injury or elevation of the content of IL-1 beta or Toll-like receptor 4 in sham rats. In Nx, hypoxia also extended to the cortical area without ameliorating the peritubular capillary rarefaction but, unexpectedly, attenuated hypertension, inflammation, innate immunity activation, renal injury, and oxidative stress. The present study, in disagreement with current concepts. shows evidence that hypoxia exerts a renoprotective effect in the Nx model instead of acting as a factor of renal injury. The mechanisms for this unexpected beneficial effect are unclear and may involve NF-kappa B inhibition, amelioration of oxidative stress, and limitation of angiotensin II production by the renal tissue. (AU)

• Processo FAPESP: 12/10926-5 - Patogênese e terapêutica da doença renal crônica: papel da imunidade inata na lesão de glomérulos, túbulos e interstício
• Beneficiário: Roberto Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/26726-8 - Papel da hipóxia na ativação da imunidade inata na progressão da doença renal crônica associada ao modelo de ablação renal de 5/6
• Beneficiário: Lisienny Campoli Tono Rempel
• Modalidade de apoio: Bolsas no Brasil - Doutorado