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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
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YAP mediates the interaction between the Hippo and PI3K/Akt pathways in mesangial cell proliferation in diabetic

Xuan Qian1, Linlin He1, Meng Hao1

  • 1Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.

Acta Diabetologica
|August 21, 2020
PubMed
Abstract

Insights

Diabetic conditions inhibit the Hippo pathway, activating YAP and promoting mesangial cell proliferation. The PI3K/Akt pathway further exacerbates this by inhibiting the Hippo pathway, accelerating diabetic nephropathy.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Endocrinology

Background:

  • Glomerular mesangial cell (MC) proliferation is a key feature of diabetic nephropathy (DN).
  • The Hippo and PI3K/Akt signaling pathways regulate MC proliferation, but their interplay in hyperglycemia-induced DN is unclear.

Purpose of the Study:

  • To elucidate the relationship between the Hippo and PI3K/Akt pathways in the context of diabetic nephropathy.
  • To investigate the role of YAP and PTEN in hyperglycemia-induced MC proliferation.

Main Methods:

  • Diabetic nephropathy model using db/db mice and high-glucose-cultured mesangial cells.
  • Investigated PI3K/Akt pathway linkage to the Hippo pathway via MST1 using knockdown plasmids.
  • Utilized LY294002 and SC79 to assess PI3K/Akt pathway roles and RNA silencing/overexpression of YAP and PTEN.

Main Results:

  • Decreased MST1/Lats1 phosphorylation and increased PI3K/Akt activation observed in DN models, correlating with MC proliferation.
  • Gene silencing confirmed PI3K/Akt pathway's intervention in the Hippo pathway.
  • YAP was found to regulate PI3K/Akt via PTEN.

Conclusions:

  • Diabetic conditions inhibit the Hippo pathway, leading to YAP activation and MC proliferation.
  • YAP inhibits PTEN, activating the PI3K/Akt pathway, which in turn further inhibits the Hippo pathway.
  • This positive feedback loop accelerates MC proliferation and diabetic nephropathy progression.
Keywords:
Diabetic nephropathyHippo pathwayMesangial cellsPI3KProliferationYAP

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