AI Article Synopsis
- Podocyte injury and loss are key features of diabetic nephropathy (DN), but the exact molecular mechanisms are still unclear.
- The study found that increased phosphorylation and reduced nuclear localization of YAP, a transcriptional coactivator, in podocytes is linked to diabetic kidney damage in mice and humans.
- Knocking out the Yap gene in podocytes worsens kidney injury, indicating that targeting the Hippo pathway could lead to new treatments for diabetic nephropathy.
Article 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 (Yap) 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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| http://dx.doi.org/10.1016/j.kint.2024.01.038 | DOI Listing |
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