Process of keratinization

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Dr. Madhulika Mhatre JR-3 Dept of Dermatology

Introduction

Skin consists of a tough connective tissue, the dermis, overlaid by a multilayered waterproof epithelium, the epidermis. The epidermis is continually renewed from stem cells,with a turnover time of 59-75 days

26-42 days :transit through str.malpigii 14days: transit through str. corneum

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Functions Of The Epidermis

- Chemical - Biological - Temperature - Mechanical

Protect body homeostasis - Temperature regulation - Prevent fluid loss

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Form a protective barrier from physical insults

Characteristics Of The Epidermis

TISSUE RENEWAL : Continuous selfrenewal of keratinocytes STRENGTH : Both intracellular and intercellular strength CORNIFICATION : Process that creates a water impermeable barrier

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Self-renewing tissue requires

A highly regulated process that balances cellular proliferation and cell death The epidermis is continuously renewed from stem cells which are present at the base of rete ridges of interfollicular epidermis

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REGULATION OF EPIDERMOPOESIS

STIMULATORY FACTORS

TRANSFORMING GROWTH FACTOR ALPHA AMPHIREGULIN INTERLEUKIN 1 AND 6 GM- CSF KGF (dermal fibroblasts) VITAMIN A AND RETINOIC ACIDS INHIBITORY FACTORS INTERFERON ALPHA AND GAMMA

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HUMAN EPIDERMAL GROWTH FACTOR

Stem cells

and have the ability to divide throughout the organisms lifetime, yielding progeny that differentiate and others that remain stem cells. The epidermal stem cells lie in the basal layer, attached to the basal lamina. They progressively differentiate, switching from expression of one set of keratins to expression of another until, eventually, their

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Stem cells are not terminally differentiated

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The stem cells seem to be clustered near the tips of the dermal papillae and base of rete ridges. They divide giving rise (through a sideways movement) to transit amplifying cells. The transit amplifying cells divide frequently, and begin to differentiate and slip out of the basal layer
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Keratinocyte proliferation

in normal epidermis, all TA cells remain attached to basement membrane transition from stem cell to TA cell is the first step in keratinocytes differentiation

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most of the proliferation is by transient amplifying cells (TA cells)

Epidermal proliferation

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TA cells migrate laterally along the basement membrane

Epidermal proliferation

Proceed towards terminal differentiation

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Once TA cells stop proliferating, they lose their attachment to the basement membrane

LAYERS OF EPIDERMIS

STRATUM LUCIDUM STRATUM GRANULOSUM STRATUM SPINOSUM STRATUM BASALE

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STRATUM CORNEUM

Keratinocyte morphology and function

Stratum spinosumcells increase in size, increased cytoplasm:nucleus ratio, cell layer4-6 cells thick, no further cell division Stratum granulosumcells become elongated, usually 1-2 cell layers thick, accumulate amorphous keratohyaline granules Stratum corneum keratinocytes contain thickened cell envelopes, contain no nucleus, imbedded in lipid matrix

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Stratum basalecuboidal cells, cells within this layer proliferate, all cells attached to the basement membrane, one cell layer thick.

Stratum basale

These cell divide by mitosis to renew the entire population of keratinocytes, replacing the dead cells that are lost from the skin surface. The nucleus is large and mitotic figures are numerous. The cytoplasm is basophilic due to ribosomes and tonofilaments occuring singly or in bundles.

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Single layer of cuboidal or columnar cells, on basal lamina.

Stratum spinosum

A layer of polyhedral shaped cells, flattened parallel to the surface, with central nuclei that are slightly flattened. The adjacent cells extend numerous processes toward each other that attach by desmosomes. Thus, each cell appears "spiny", giving rise to the name spinosum. The cytoplasm contains the same organelles as Basale cells, but with distinctive lamellated granules or membrane-coating granules (ODLAND BODIES)
Ovoid, membrane bound granule, 0.1-0.5um in diameter, containing parallel lamellae orientated transverse to the long axis of the granule.

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Stratum granulosum:

Three to 5 layers of flattened cells, with irregular, large keratohyalin granules. Granules, 1-5um in diameter, have no membrane and consist of closely packed 2nm subunits. The granules are associated with tonofilaments, which may pass through or be partially embedded.

Two kinds of granules, small dense homogeneous deposits, and large irregular keratohyalin granules containing histidine-rich protein, RNA, proteoglycans and lipid.

Keratohyalin forms dense cytoplasmic granules that promote dehydration of the

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Stratum lucidum:

Few cells thick, and seen in palms and soles Cells are refractile, eosinophilic or unstained. There is no nucleus and the cytoplasm is almost fully keratinized.
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Stratum corneum:

All the cytoplasm is replaced by 8-10nm filaments of keratin embedded in an amorphous filaggrin matrix. Cell membrane is thickened by deposition of nonkeratin material on inner aspect of membrane (cornified envelope). The intercellular space is filled by material from lamellar granules.

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Many layers of flattened cornified, or keratinized cells.

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Keratinization

Formation of keratin within the keratinocytes KERATINS: filamentous skeleton of all cells comprises of Actin, tubulin and intermediate filaments

Epithelial cells- Keratin is the intermediate filament

keratin filaments extend from the nuclear membrane to desmosomal plaques at the cell membrane keratins enable keratinocytes to sustain mechanical and non-mechanical stress
KERATIN INSOLUABLE PROTEIN

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Cornification
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process that begins in cells of the upper spinous layers the induction of proteins forming the cornified cell envelope and lipid barrier dependent on calcium

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At the molecular level, the cornified envelope is formed by proteins that are highly crosslinked by transglutaminases, with specific lipids on the outside

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Steps

Spinous layer- INITIATION

Granular layer-REINFORCEMENT

Loricrin and SPRs crosslinked by TG1 & TG3 Lipids from lamellar bodies are attached to above crosslinked proteins- LIPID BILAYER

Corneum

Crosslinking of fillagrin bound keratin filaments and other proteins

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Envoplakin, periplakin and involucrin crosslinked by TG 1 &5 over the desmosomes- scaffold for CE

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Lipid Barrier

The lipid composition and moisture content change with increasing differentiation Stored in the Odland bodies which are the precursors of the skin-specific barrier lipids in the form of lamellar bilayer lipid membranes. Stability Desquamation Permeability barrier

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FORMATION AND FUNCTION OF THE EPIDERMAL LIPIDS

2- Keratinocyte 3- Exocytosis 4- Epidermal lipids 5- Horny cells

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1- Odland body with bilayer membrane

COMPOSITION OF THE EPIDERMAL LIPIDS

Ceramides (40%) - barrier-forming and moisture-binding functions FFA (25%) Cholesterol (25%) Cholesteryl sulphate.
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THE PERMEABILITY BARRIER

It prevents invasion by microorganisms and certain substances such as chemicals and allergens. It minimizes transepidermal water loss (TEWL) and thus protects the body from dehydration.

Natural moisturizing factors (NMF)

Substances, which occur naturally in the body and retain water in the horny layer, are called natural moisturizing factors (NMF). They originate from the cornification process (differentiation) of keratinocytes and from sweat and sebum

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The ability of the skin to store water depends in large part on the make-up of the barrier lipids in the horny layer.

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T H A N K Y O U

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