Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis

Xiao-Mei Wang1, Min Yao, Shu-Xia Liu

  • 1Dept. of Pathology, Third Hospital, Hebei Medical Univ., No. 139 Ziqiang Rd., Shijiazhuang, Hebei, China 050051. alan846829@163.com.

Insights

High glucose triggers podocyte apoptosis in diabetic nephropathy. The PI3K/Akt and Notch pathways play crucial roles in this process, offering potential therapeutic targets for kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Podocyte apoptosis is a key factor in diabetic nephropathy (DN) pathogenesis.
  • The precise mechanisms underlying high glucose (HG)-induced podocyte apoptosis are not fully understood.

Purpose of the Study:

  • To investigate the roles of the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis.
  • To explore potential therapeutic interventions targeting these pathways in diabetic nephropathy.

Main Methods:

  • Cultured conditionally immortalized mouse podocytes in high glucose medium.
  • Utilized chemical inhibitors and short-hairpin RNA (shRNA) to modulate Notch and PI3K/Akt pathways.
  • Assessed protein and gene expression via Western blotting and real-time PCR.
  • Quantified podocyte apoptosis using TUNEL and Annexin V/PI staining.

Main Results:

  • PI3K/Akt pathway activation inhibited podocyte apoptosis during early high glucose exposure.
  • Notch pathway activation was implicated in podocyte apoptosis during later stages of high glucose exposure.
  • Inhibiting the Notch pathway or activating the PI3K/Akt pathway reduced apoptosis in HG-treated podocytes.

Conclusions:

  • The Notch and PI3K/Akt signaling pathways are critically involved in mediating high glucose-induced podocyte apoptosis.
  • Modulating these pathways presents a potential therapeutic strategy for diabetic nephropathy.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.2K
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.6K
Notch Signaling Pathway03:14

Notch Signaling Pathway

4.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.2K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
4.7K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.2K