fibroblast apoptotic process

Definition

Target type: biologicalprocess

Any apoptotic process in a fibroblast, a connective tissue cell which secretes an extracellular matrix rich in collagen and other macromolecules. [CL:0000057, GOC:jl, GOC:mtg_apoptosis, GOC:yaf]

Fibroblast apoptosis is a tightly regulated process that eliminates damaged or unwanted cells. It involves a series of biochemical events leading to cell death characterized by distinct morphological and molecular changes. Here's a detailed description:

**1. Initiation:** Apoptosis can be triggered by various stimuli, including:

* **Extracellular Signals:**
* **Growth factor withdrawal:** Lack of essential growth factors like fibroblast growth factor (FGF) or platelet-derived growth factor (PDGF) can initiate apoptosis.
* **Death receptor activation:** Binding of ligands like TNF-alpha or Fas ligand to their respective death receptors (TNF receptor or Fas receptor) on the fibroblast surface activates the apoptotic cascade.
* **DNA damage:** Exposure to damaging agents like radiation or cytotoxic drugs can cause DNA damage, triggering apoptosis.
* **Intracellular Signals:**
* **Mitochondrial dysfunction:** Stressful conditions can disrupt mitochondrial function, leading to the release of pro-apoptotic proteins like cytochrome c.
* **Endoplasmic reticulum (ER) stress:** Accumulation of unfolded proteins in the ER triggers a stress response that can culminate in apoptosis.

**2. Execution Phase:**

* **Caspase activation:** The key executioners of apoptosis are a family of cysteine proteases called caspases. Upon receiving apoptotic signals, initiator caspases (caspase-8 or caspase-9) are activated. These then activate effector caspases (caspase-3, -6, and -7), which cleave various cellular substrates.
* **Mitochondrial outer membrane permeabilization (MOMP):** Pro-apoptotic signals trigger the release of cytochrome c from mitochondria. Cytochrome c binds to apoptotic protease-activating factor 1 (Apaf-1), which then recruits caspase-9, forming the apoptosome. The apoptosome activates caspase-9, initiating the caspase cascade.
* **DNA fragmentation:** Caspases activate DNA fragmentation factors (DNases) that cleave the DNA into distinct fragments, resulting in the characteristic DNA ladder pattern observed during apoptosis.

**3. Cell Death:**

* **Blebbing:** The cell membrane forms blebs, or small bulges, due to cytoskeletal rearrangements.
* **Apoptotic body formation:** The cell shrinks and breaks down into smaller fragments called apoptotic bodies containing cellular organelles and nuclear material.
* **Phagocytosis:** Apoptotic bodies are quickly engulfed and degraded by neighboring cells or macrophages, preventing the release of inflammatory contents.

**4. Key Molecular Players:**

* **Bcl-2 family proteins:** This family comprises both pro-apoptotic and anti-apoptotic proteins. They regulate the release of cytochrome c from mitochondria, playing a crucial role in MOMP.
* **Caspases:** A family of proteases that execute the apoptotic program by cleaving various cellular substrates.
* **DNA fragmentation factors:** Nucleases that cleave DNA into distinct fragments.
* **Apoptotic signaling pathways:** Numerous signaling pathways converge on the apoptotic machinery, regulating the execution of apoptosis.

**5. Physiological Relevance:**

Fibroblast apoptosis plays a crucial role in tissue homeostasis, development, and wound healing. It eliminates damaged or unwanted cells, preventing the accumulation of potentially harmful cells. It also contributes to the proper remodeling of tissues during development and repair.

**6. Dysregulation in Disease:**

Deregulation of fibroblast apoptosis can contribute to various pathological conditions:

* **Cancer:** Inhibition of apoptosis allows cancer cells to survive and proliferate uncontrollably.
* **Autoimmune diseases:** Excessive apoptosis of fibroblasts can contribute to tissue damage and inflammation.
* **Fibrotic diseases:** Overactive fibroblast proliferation and reduced apoptosis can lead to excessive scar tissue formation.

Understanding the intricate mechanisms of fibroblast apoptosis is essential for developing therapeutic strategies targeting this process in various diseases.'
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Proteins (5)

Compounds (229)