Written by Angelyn Evan S. Bomediano

I.   Keratinocytes (KC)

A. Definition

Keratinocytes are the typical type of cell in the epidermis, the top layer of skin. They make up about 90% of the cells in the epidermis. They start in the stratum basale, the deepest layer, and move up to the stratum corneum, the outermost part. Also, they are flat, squamous cells with a lot of keratin but no nucleus.

They accumulate in the basal layer and change as they move toward the skin’s surface. This process is gradual differentiation. It changes shape and starts making keratin, cytokines, growth factors, interleukins, and complement factors. Moreover, it is under control by several factors and mechanisms that work on the epigenome.

B.  Function

Keratinocytes have a particular job to do. They are essential for protection and this is due to their formation, a tight barrier that keeps foreign substances from getting into the body and keeps moisture, heat, and other vital things from escaping.

These cells also have a structural role, forming tight bonds with the other cells in the epidermis and maintaining them in their locations. KC also acts as an immune system regulator when the skin hurts.

C.  Applications

1. Keratinocyte Cell Culture

Rheinwald and Green were the first people 30 years ago to write about developing human KC in a single layer. Since then, there have been many improvements in how human keratinocytes are grown. They can now be in both two-dimensional and three-dimensional cultures.

Normal Human Epidermal Keratinocytes (NHEK) can be from a young person’s foreskin or normal human tissue on an adult’s face, breast, abdomen, or thighs, among other places. NHEK from a single donor or a group of donors can be for research uses. The right amount of calcium in the culture is vital to ensure that KC can grow and change in the best way.

2.  Characterization

Keratinocytes express specific keratins at each stage of differentiation and other markers like involucrin, loricrin, transglutaminase, filaggrin, and caspase 14.

3.  Applications of Research

KC are available for many things, like studying how the epidermis grows and changes, how the body take in drugs, testing cosmetics and toxins, and analyzing how integument ages. They are also available in skin research, how wounds heal, and cancer research.

D.  Interactions with other Cells in the Skin

1. Keratinocytes and Fibroblasts

Cross-talk between KC and fibroblasts is essential for keeping the skin balanced and healing wounds. Paracrine signaling is how these two types of cells interact with each other. Interrupting this cross-talk can cause chronic injuries.

2.  Keratinocytes and Melanocytes

KC and melanocytes need to communicate for the epidermis to stay in balance. Melanocytes make melanin, which soaks up UV waves and keeps KC’s DNA from getting damaged. On the other hand, KC helps melanocytes multiply, change, and make more melanin.

3.  Keratinocytes and other cells

KC works with lymphocytes and cellular Langerhans in the integument to change how the immune system works.

E.  Role in wound healing and inflammation

1. Keratinocytes in Wound Healing

KC is in charge of repairing damage to the epidermis. It is called “re-epithelialization,” and a wound must heal. When the skin undergoes stress, KC becomes active, moves to the injury, and starts making more of themselves to fill the hole.

When an injury is healing, KC, fibroblasts, and immune cells need to communicate. When KC doesn’t work right, wounds don’t heal and stay open for a long time.

2.  Keratinocytes in Inflammation

When the epidermal barrier breaks or pathogens get into the skin, the body responds with inflammation. Keratinocytes participate in this process because they make cytokines, which send signals to immune cells that can be good or bad.

Keratinocytes also play a role in several allergic skins diseases and chronic inflammatory conditions like psoriasis because they can recruit and activate dendritic cells and leukocytes.

II.   Keratin (K)

1. Definition

Keratin is a type of protein seen in hair, skin, and nails. K is a potent, fibrous protein that can’t be scratched or torn. It is also called an intermediate filament, an essential protein that gives the structure of hair, skin, and nails.

Like other proteins, keratin rises from amino acids. Each protein possesses its own set of amino acids, like each person has deoxyribonucleic acid (DNA). Though keratin can be in organs and glands, it is in cells that line the inside of the body. Endothelial cells cover the body’s surface.

K also includes the digestive and urinary tracts, both inside the body but opening to the outside world. K can withstand different environmental conditions because it is strong and has a solid structure.

B.  Location

Keratin is in the top layer of skin, called the epidermis. The integument is the biggest organ in the body, and it protects the organs inside it. New skin comes from the bottom of the epidermis while the old ones rise to the top and fall off. What’s left of dead skin tissue is usually a mix of proteins, with keratin being the main one. In this way, most surface-level parts of the epidermis are composed of the keratin epidermis’s keratin cells.

C.  Types of Keratin

There are 54 types of keratin protein in the body. The main four types are:

• Type I – The proteins in type I K are usually small and acidic. Acidic molecule can either give another molecule a proton (hydrogen ion) or form a covalent bond with an electron pair. Covalent bonds happen when two molecules share electrons. This type is significant to the health of epithelial cells.
• Type II – Keratins of type II are large proteins that have a pH of 7.
• Alpha-keratin – Alpha-keratins are in humans and the wools of other mammals. Since they are fibrous and helical, this type helps keep the structure of epithelia cells strong.
• Beta-keratin – Only birds and reptiles have beta-keratins. They help to keep the shape of:
  • Claws
  • Scales
  • Beaks
  • Skin
  • Feathers

D.  Keratin Structure

The structure and function of keratin depend on what amino acids are in it. The shape of a protein molecule depends on the kinds of amino acids and how they connect. The same protein molecule can have more than one structure:

Primary structure: The order of amino acids within one protein molecule

Secondary structure: Amino acids bond together to form an alpha-helix (coil shape) or beta- pleated sheet (accordion shape)

Tertiary structure: One port of a protein chain binds with another part of the same chain

Quarternary structure: A complex protein structure where more than one protein chain binds to another

Due to its robust and stable structure, Keratin is insoluble in water and cannot affect acids, alkalis, or other powerful solvents. As a result, keratin can withstand circumstances both within and outside the human body. Keratin shrinks when exposed to water at high temperatures because some bonds break because to the high heat.

E.  Function

Keratin controls epithelial cells’ formation and protection, strengthening the skin and supporting internal organs. It also keeps the skin elastic and preserves the skin’s suppleness. Additionally, it binds epithelial cells together and assists them in resisting the effects of mechanical stress.

What do keratinocytes contain?

KC develops in the basal layer of the epidermis and differentiates as they rise. During this process, they change their shape and start to produce keratin, cytokines, growth factors, interleukins, and complement factors. Several factors and epigenetic pathways influence KC differentiation.

A.  Keratin

KC produces keratin that makes up most of the structure of the skin, hair, and nails.

This component has an essential role in mediating cutaneous immune responses, inflammation, wound healing, and the growth and development of certain neoplasms.

B.  Cytokines

KC is known to produce cytokines as well. That said, cytokines regulate immune and inflammatory responses and play essential roles in pathological skin conditions.

C.  Growth Factors

KGF (Keratinocyte Growth Factor), also known as FGF7, promotes the migration and differentiation of epithelial cells and protects them against stress. KGF is generated by mesenchymal cells and exerts its biological effects by binding to its high-affinity receptor, a splice variant of FGF receptor 2 (FGFR2-IIIb), expressed by epithelial cells, including epidermal keratinocytes.

D.  Interleukins

Despite being given less attention, keratinocytes also produce a variety of cytokines, including interleukin (IL)-1, -6, -7, -8, -10, -12, -15, -18, and -20, as well as tumor necrosis factor-alpha (TNF). Wherein (IL)-1, -6, -8, and TNF were discovered and investigated.

E.  Complement Factors

KC is the predominant cell type in the skin; this cell type produces two soluble components of the complement system, C3 and factor B.

F.  Others

Also produce eicosanoids, prostaglandin (PG) E2, and neuropeptides such as proopiomelanocortin and α MSH.

What is the difference between keratinocytes and melanocytes?

Keratinocytes refer to the epidermal cells that produce keratin, while Melanocytes refer to the mature melanin-forming cells in the skin. In terms of its differentiation, KC is from the basal layer of the epithelium.

At the same time, Melanocytes are from the neural crest cells. With regards to their production, KC is more on the display of Keratin which most of the epidermal cells are, while Melanocytes are on the production of Melanin, and it is lesser compared to the keratinocytes.

Moreover, KC is a physical barrier between organisms and the external environment and forms hair and nails. While the other is responsible for the color of the skin.

Where are the oldest keratinocytes in your skin found?

The oldest KC in the skin is at the outermost epidermal layers, the Stratum corneum. This comprises around 25-50 layers of KC filled with keratin continuously shedding off. Furthermore, the constant exertion of friction stimulates cell production in this layer and the production of callus.

Do keratinocytes produce vitamin D?

Yes, KC produces vitamin D. Besides that, they contain enzymatic machinery to convert vitamin D to active metabolites 1,25(OH)2D. In particular, the vitamin D receptor (VDR) allows the keratinocytes to respond to the 1,25(OH)2D.

Vitamin D and its receptors influence various skin activities such as inhibition of proliferation, encouragement of differentiation, including the creation of the permeability barrier, enhancement of innate immunity, hair follicle cycle modulation, and tumor suppression.

Do keratinocytes produce melanin?

Currently, some researchers discovered that melanin undergoes concentration in keratinocytes in the stratum basale, the deepest layer of integument and that the number of melanin granules correlates with complexion. Their findings revealed how melanin scatters within KC in different integument phototypes.

Previous research also revealed that melanosomes in dark skin occur as single membrane- delimited structures. In contrast, melanosomes in light skin only exist as clusters surrounded by a membrane.

What holds keratinocytes together in the epidermis?

The structures of resistance in the epidermis are the desmosomes, which allow the keratinocytes to stick to each other. The function of sticking together is possible by how the desmosomal molecules and cytoskeletal filaments work together. Moreover, whenever the skin undergoes physical trauma and rubbing, the desmosomes, connecting junctions in-between, help keep the cells together.

What are nucleated keratinocytes?

Normal KC is usually flat, keratinized squamous, and nucleus-free. With that, nucleated ones are known to be abnormal. However, it occurs seldomly. Moreover, it includes inflammatory cells and indicates parakeratosis, erosions, or that the sample was taken from below the stratum corneum.

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