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UCP2-dependent improvement of mitochondrial dynamics protects against acute kidney injury.
Qin, Nan; Cai, Ting; Ke, Qingqing; Yuan, Qi; Luo, Jing; Mao, Xiaoming; Jiang, Lei; Cao, Hongdi; Wen, Ping; Zen, Ke; Zhou, Yang; Yang, Junwei.
Afiliação
  • Qin N; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Cai T; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Ke Q; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Yuan Q; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Luo J; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Mao X; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Jiang L; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Cao H; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Wen P; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Zen K; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Advanced Institute of Life Sciences, Nanjing, PR China.
  • Zhou Y; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
  • Yang J; Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, PR China.
J Pathol ; 247(3): 392-405, 2019 03.
Article em En | MEDLINE | ID: mdl-30426490
ABSTRACT
Acute kidney injury (AKI) is a public health concern, with high morbidity and mortality rates in hospitalized patients and because survivors have an increased risk of progression to chronic kidney disease. Mitochondrial damage is the critical driver of AKI-associated dysfunction and loss of tubular epithelial cells; however, the pathways that mediate these events are poorly defined. Here, in murine ischemia/reperfusion (I/R)-induced AKI, we determined that mitochondrial damage is associated with the level of renal uncoupling protein 2 (UCP2). In hypoxia-damaged proximal tubular cells, a disruption of mitochondrial dynamics demonstrated by mitochondrial fragmentation and disturbance between fusion and fission was clearly indicated. Ucp2-deficient mice (knockout mice) with I/R injury experienced more severe AKI and mitochondrial fragmentation than wild-type mice. Moreover, genetic or pharmacological treatment increased UCP2 expression, improved renal function, reduced tubular injury and limited mitochondrial fission. In cultured proximal tubular epithelial cells, hypoxia-induced mitochondrial fission was exacerbated in cells with UCP2 deletion, whereas an increase in UCP2 ameliorated the hypoxia-induced disturbance of the balance between mitochondrial fusion and fission. Furthermore, results following modulation of UCP2 suggested it has a role in preserving mitochondrial integrity by preventing loss of membrane potential and reducing subsequent mitophagy. Taken together, our results indicate that UCP2 is protective against AKI and suggest that enhancing UCP2 to improve mitochondrial dynamics has potential as a strategy for improving outcomes of renal injury. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Injúria Renal Aguda / Proteína Desacopladora 2 / Mitocôndrias Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: J Pathol Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Injúria Renal Aguda / Proteína Desacopladora 2 / Mitocôndrias Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: J Pathol Ano de publicação: 2019 Tipo de documento: Article