positive regulation of podocyte apoptotic process

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of glomerular visceral epithelial cell apoptotic process. [GO_REF:0000058, GOC:TermGenie, PMID:23692924]

Positive regulation of podocyte apoptotic process involves a complex interplay of signaling pathways that ultimately lead to the programmed death of podocytes, specialized cells in the kidney that form the filtration barrier. This process is tightly regulated and can be triggered by various stimuli, including:

- **Mechanical stress:** High blood pressure or glomerular hyperfiltration can damage the podocyte cytoskeleton and trigger apoptosis.
- **Immune dysregulation:** Autoantibodies against podocyte antigens can initiate apoptosis, leading to immune-mediated glomerular diseases.
- **Metabolic stress:** Conditions such as diabetes and hyperglycemia can induce oxidative stress and inflammation in podocytes, contributing to their demise.

The following pathways play key roles in positive regulation of podocyte apoptosis:

- **Intrinsic pathway:** This pathway is activated by intracellular stress signals, such as DNA damage or protein misfolding. Activation of the Bcl-2 family proteins, including Bax and Bak, leads to mitochondrial membrane permeabilization and release of cytochrome c. This triggers the formation of the apoptosome, which activates caspases, ultimately leading to apoptotic cell death.
- **Extrinsic pathway:** This pathway is initiated by extracellular signals, such as death receptor ligands (e.g., TNF-α, Fas ligand). Binding of these ligands to their respective death receptors activates caspase-8, which can either directly activate executioner caspases or activate the intrinsic pathway via Bid cleavage.
- **Growth factor withdrawal:** Podocytes require specific growth factors, such as VEGF and PDGF, for survival. Withdrawal of these factors can trigger apoptosis through the activation of the p53 pathway, leading to cell cycle arrest and eventually death.
- **Oxidative stress:** Reactive oxygen species (ROS) produced by mitochondrial dysfunction or other stimuli can damage podocyte DNA and proteins, triggering apoptosis via the intrinsic pathway.
- **Inflammation:** Inflammatory mediators, such as TNF-α and IL-1β, can activate pro-apoptotic signaling pathways and promote podocyte apoptosis.

The loss of podocytes due to apoptosis contributes to glomerular scarring and ultimately leads to progressive kidney disease. Therefore, understanding the mechanisms underlying positive regulation of podocyte apoptosis is crucial for developing therapeutic strategies aimed at preventing podocyte loss and protecting kidney function.'
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Proteins (1)

Compounds (13)