Inhibition of transcriptional coactivator YAP Impairs the expression and function of transcription factor WT1 in diabetic podocyte injury.
Kidney Int
; 105(6): 1200-1211, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38423183
ABSTRACT
Podocyte injury and loss are hallmarks of diabetic nephropathy (DN). However, the molecular mechanisms underlying these phenomena remain poorly understood. YAP (Yes-associated protein) is an important transcriptional coactivator that binds with various other transcription factors, including the TEAD family members (nuclear effectors of the Hippo pathway), that regulate cell proliferation, differentiation, and apoptosis. The present study found an increase in YAP phosphorylation at S127 of YAP and a reduction of nuclear YAP localization in podocytes of diabetic mouse and human kidneys, suggesting dysregulation of YAP may play a role in diabetic podocyte injury. Tamoxifen-inducible podocyte-specific Yap gene knockout mice (YappodKO) exhibited accelerated and worsened diabetic kidney injury. YAP inactivation decreased transcription factor WT1 expression with subsequent reduction of Tead1 and other well-known targets of WT1 in diabetic podocytes. Thus, our study not only sheds light on the pathophysiological roles of the Hippo pathway in diabetic podocyte injury but may also lead to the development of new therapeutic strategies to prevent and/or treat DN by targeting the Hippo signaling pathway.
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MEDLINE
Assunto principal:
Fosfoproteínas
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Fatores de Transcrição
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Transdução de Sinais
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Camundongos Knockout
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Proteínas WT1
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Proteínas Adaptadoras de Transdução de Sinal
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Diabetes Mellitus Experimental
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Nefropatias Diabéticas
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Podócitos
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Proteínas de Sinalização YAP
Idioma:
En
Revista:
Kidney Int
Ano de publicação:
2024
Tipo de documento:
Article