keratinocyte proliferation

Definition

Target type: biologicalprocess

The multiplication or reproduction of keratinocytes, resulting in the expansion of a cell population. Keratinocytes are epidermal cells which synthesize keratin and undergo a characteristic change as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. [CL:0000311]

Keratinocyte proliferation is a fundamental process in maintaining the integrity of the epidermis, the outermost layer of skin. It involves a tightly regulated series of events that ensure the continuous renewal of skin cells. The process begins with basal keratinocytes, located in the stratum basale, the deepest layer of the epidermis. These cells are mitotically active and continuously divide to generate new keratinocytes. As new cells are produced, they migrate upwards through the epidermal layers, undergoing a process known as differentiation. This differentiation involves the expression of specific proteins, such as keratins, which contribute to the structural integrity and barrier function of the skin. During their upward migration, keratinocytes undergo a series of changes, including:

* **Increased expression of keratin proteins:** Keratins are fibrous proteins that provide structural support to the skin. As keratinocytes differentiate, they express increasing amounts of keratins, forming the characteristic cytoskeletal framework of the epidermis.
* **Formation of desmosomes:** These specialized cell junctions help to bind keratinocytes together, providing mechanical strength and stability to the skin.
* **Accumulation of lipids:** Keratinocytes synthesize and accumulate lipids, primarily ceramides, which form the skin's barrier function, protecting the body from external insults like water loss and pathogens.
* **Nucleus degradation:** As keratinocytes reach the outermost layer of the epidermis, the stratum corneum, their nuclei degrade, and the cells become flattened and tightly packed, forming the protective barrier layer of the skin.

The entire process of keratinocyte proliferation and differentiation is controlled by a complex interplay of signaling pathways, growth factors, and transcription factors. Some key factors involved in this process include:

* **Epidermal growth factor (EGF):** EGF is a potent mitogen that stimulates keratinocyte proliferation.
* **Transforming growth factor-alpha (TGF-α):** Like EGF, TGF-α promotes keratinocyte proliferation and differentiation.
* **Fibroblast growth factor (FGF):** FGFs are a family of growth factors that play diverse roles in skin development and wound healing, including regulating keratinocyte proliferation and differentiation.
* **Wnt signaling pathway:** This pathway is involved in the regulation of cell fate, proliferation, and differentiation, playing a crucial role in maintaining the balance of keratinocyte populations in the epidermis.
* **Sonic hedgehog (Shh) signaling pathway:** Shh signaling regulates epidermal stem cell proliferation and differentiation.

Proper keratinocyte proliferation and differentiation are essential for skin health. Dysregulation of this process can lead to various skin disorders, including psoriasis, eczema, and skin cancer. Understanding the mechanisms underlying keratinocyte proliferation is crucial for developing effective therapies for these conditions.'
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Compounds (46)