positive regulation of hepatocyte proliferation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of hepatocyte proliferation. [GOC:BHF, GOC:mah]

Positive regulation of hepatocyte proliferation is a complex process involving multiple signaling pathways and transcription factors that promote the growth and division of liver cells. It is essential for liver regeneration after injury, but dysregulation of this process can contribute to liver disease.

**Growth factors and signaling pathways:**

* **Hepatocyte growth factor (HGF):** A key regulator of hepatocyte proliferation, HGF binds to its receptor, c-Met, on the cell surface, activating downstream signaling pathways, including the RAS/MAPK and PI3K/AKT pathways. These pathways promote cell survival, proliferation, and migration.
* **Transforming growth factor-alpha (TGF-alpha):** Another important growth factor, TGF-alpha activates the EGFR signaling pathway, leading to similar effects as HGF.
* **Interleukin-6 (IL-6):** A cytokine involved in inflammation, IL-6 can also stimulate hepatocyte proliferation, particularly in the context of liver injury. It activates the JAK/STAT pathway.
* **Wnt signaling pathway:** This pathway plays a crucial role in development and regeneration. Wnt ligands bind to their receptors, leading to the accumulation of beta-catenin in the cytoplasm, which then translocates to the nucleus and activates target genes involved in cell proliferation and differentiation.

**Transcription factors:**

* **c-Myc:** A proto-oncogene that regulates cell cycle progression and is upregulated in response to growth factor stimulation.
* **E2F:** A family of transcription factors that control the expression of genes involved in DNA replication and cell cycle progression.
* **STAT3:** A transcription factor activated by IL-6 and other cytokines, it promotes cell survival and proliferation.
* **NF-κB:** A transcription factor involved in inflammation and immune responses. It can also regulate hepatocyte proliferation.

**Other mechanisms:**

* **Cell cycle regulation:** Positive regulation of hepatocyte proliferation involves the coordinated activation of cell cycle checkpoints and the expression of cyclin-dependent kinases (CDKs) and cyclins, which promote cell cycle progression.
* **Extracellular matrix remodeling:** The extracellular matrix surrounding hepatocytes undergoes changes during proliferation, facilitating cell migration and growth.

**Dysregulation and disease:**

* **Excessive proliferation:** Uncontrolled hepatocyte proliferation can lead to liver hyperplasia, which can predispose to liver cancer.
* **Defective proliferation:** Reduced hepatocyte proliferation can impair liver regeneration and contribute to liver fibrosis and cirrhosis.

Overall, positive regulation of hepatocyte proliferation is a complex and tightly regulated process essential for liver homeostasis. Dysregulation of this process can have significant consequences for liver health.'
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Proteins (4)

Compounds (30)