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Skin Keratinization & Its Disorders
Keratinization, also termed as cornification, is a process of
cytodifferentiation which the keratinocytes undergo…
…when proceeding from their post-germinative state (stratum
basale) to finally differentiated, hardened cell filled with
protein…
…constituting a structurally and functionally distinct keratin-
containing surface layer known as stratum corneum.
DEFINITION
LAYERS OF EPIDERMIS
CELL KINETICS
• Epidermal keratinization occurs between 22 and 24 weeks of
gestation.
• It begins on the head, face, palms and soles.
• The 4 layers of the epidermis are divided into 2 functional
compartments:
1. Proliferative compartment (cell cycle = 13 days)
2. Differentiated compartment (cell cycle = 12 days)
• Cornified layer compartment (cell cycle = 14 days)
• The epidermal turnover time is therefore 39 days (13+12+14)
CELL GENETICS
• To maintain proliferative of stem cells, p63 gene is needed.
• To trigger differentiation, an increase in EC calcium is needed.
• To maintain differentiation, △Np63α (isoform of p63) and
Notch signaling pathway are needed.
FACTORS INFLUENCING DIFFERENTIATION
1. Stimulatory signals
EGF, KGF (Amphiregulin),TGF-α, IL-1, IL-6, GM-CSF
2. Inhibitory signals
TGF-β, IFN-α, IFN-γ, TNF-α
3. Signal transduction pathways
C-AMP, Protein kinase C, inositol phosphate
1. Integrins
2. Calcium (↓Ca ☞ ↓differentiation & ↑proliferation)
3. Vitamin A
4. Retinoids
KEY EVENTS IN DIFFERENTIATION
1. Formation of CK & KIF
2. Formation of desmosomes
3. Formation of keratohyaline granules
4. Odland bodies / lamellar bodies / membrane-coating granules
5. Formation of cornified envelope
1. FORMATION OF CK & KIF
1. Kera = horn
2. Keratins are a multigene family of proteins that form IF.
3. 54 functional genes code for keratins.
4. Keratin can either be acidic (Type I / 9-19 / clustered in
Chr. 17) or basic (Type II / 1-8 / clustered in Chr. 12).
5. For KIF to be formed, one acidic and one basic keratin
must combine (obligate heteropolymers)
STRUCTURE OF KERATIN
FORMATION OF KIF
DISTRIBUTION OF KIF
DISORDERS OF KERATIN
2. FORMATION OF DESMOSOMES
• Desmosomes contain two types of proteins – the transmembranous
proteins and proteins of the attachment plaque.
• The transmembranous proteins are the desmogleins and
desmocollins which are the members of the cadherin family.
• The attachment plaque proteins are desmoplakin, plakoglobin,
plakophilin, envoplakin and periplakin.
STRUCTURE OF DESMOSOME
DISORDERS OF DESMOSOME
3. FORMATION OF KERATOHYALINE GRANULES
• Main components are histidine-rich filaggrin, cystine-rich proteins
and loricin.
• Filaggrin acts as a glue and provides an amorphous matrix inside the
keratinocyte within which the KIF are embedded.
• Cystine-rich proteins will contribute to the chemical inertness and
strength of the cornified layer.
• Loricin will be a major component of the cornified envelope.
FLIAGGRIN GENE MUTATION
4. FORMATION OF ODLAND BODIES
• Has free sterols, polar lipids and hydrolytic enzymes.
• Contents are discharged into intercellular spaces.
• They form lamellae and serve as structural barrier to epidermal
permeability.
• Lipids, specially those that have linoleic acid, contribute to the
impermeability of cornified layer.
• This permeability barrier is essential for fluid and electrolyte
balance.
• It also accounts for the efficacy of topical medications, and accounts
for allergens to enter the epidermis and promote sensitization.
5. FORMATION OF CORNIFIED ENVELOPE
Skin Keratinization & Its Disorders
CALCIUM PUMP DISORDERS
KERATINIZATION IN A NUTSHELL
• Upward maturation of basal keratinocytes into cornified cells.
• Along the way:
-Cells lose their nuclei and cytoplasmic organelles
-Cells become filled inside with KIF that are embedded in the
matrix derived from keratohyaline granules.
-The plasma membrane of the cells thickens and forms an
envelope.
-Lamellar granules discharges lipids that surround the intercellular
REFERENCES
1. Rooks Textbook of Dermatology
2. Fitzpatrick’s Dermatology in General Medicine
3. Bolognia’s Dermatology
4. Moschella’s Dermatology
5. IADVL Textbook of Dermatology

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Skin Keratinization & Its Disorders

  • 2. Keratinization, also termed as cornification, is a process of cytodifferentiation which the keratinocytes undergo… …when proceeding from their post-germinative state (stratum basale) to finally differentiated, hardened cell filled with protein… …constituting a structurally and functionally distinct keratin- containing surface layer known as stratum corneum. DEFINITION
  • 4. CELL KINETICS • Epidermal keratinization occurs between 22 and 24 weeks of gestation. • It begins on the head, face, palms and soles. • The 4 layers of the epidermis are divided into 2 functional compartments: 1. Proliferative compartment (cell cycle = 13 days) 2. Differentiated compartment (cell cycle = 12 days) • Cornified layer compartment (cell cycle = 14 days) • The epidermal turnover time is therefore 39 days (13+12+14)
  • 5. CELL GENETICS • To maintain proliferative of stem cells, p63 gene is needed. • To trigger differentiation, an increase in EC calcium is needed. • To maintain differentiation, △Np63α (isoform of p63) and Notch signaling pathway are needed.
  • 6. FACTORS INFLUENCING DIFFERENTIATION 1. Stimulatory signals EGF, KGF (Amphiregulin),TGF-α, IL-1, IL-6, GM-CSF 2. Inhibitory signals TGF-β, IFN-α, IFN-γ, TNF-α 3. Signal transduction pathways C-AMP, Protein kinase C, inositol phosphate 1. Integrins 2. Calcium (↓Ca ☞ ↓differentiation & ↑proliferation) 3. Vitamin A 4. Retinoids
  • 7. KEY EVENTS IN DIFFERENTIATION 1. Formation of CK & KIF 2. Formation of desmosomes 3. Formation of keratohyaline granules 4. Odland bodies / lamellar bodies / membrane-coating granules 5. Formation of cornified envelope
  • 8. 1. FORMATION OF CK & KIF 1. Kera = horn 2. Keratins are a multigene family of proteins that form IF. 3. 54 functional genes code for keratins. 4. Keratin can either be acidic (Type I / 9-19 / clustered in Chr. 17) or basic (Type II / 1-8 / clustered in Chr. 12). 5. For KIF to be formed, one acidic and one basic keratin must combine (obligate heteropolymers)
  • 13. 2. FORMATION OF DESMOSOMES • Desmosomes contain two types of proteins – the transmembranous proteins and proteins of the attachment plaque. • The transmembranous proteins are the desmogleins and desmocollins which are the members of the cadherin family. • The attachment plaque proteins are desmoplakin, plakoglobin, plakophilin, envoplakin and periplakin.
  • 16. 3. FORMATION OF KERATOHYALINE GRANULES • Main components are histidine-rich filaggrin, cystine-rich proteins and loricin. • Filaggrin acts as a glue and provides an amorphous matrix inside the keratinocyte within which the KIF are embedded. • Cystine-rich proteins will contribute to the chemical inertness and strength of the cornified layer. • Loricin will be a major component of the cornified envelope.
  • 18. 4. FORMATION OF ODLAND BODIES • Has free sterols, polar lipids and hydrolytic enzymes. • Contents are discharged into intercellular spaces. • They form lamellae and serve as structural barrier to epidermal permeability. • Lipids, specially those that have linoleic acid, contribute to the impermeability of cornified layer. • This permeability barrier is essential for fluid and electrolyte balance. • It also accounts for the efficacy of topical medications, and accounts for allergens to enter the epidermis and promote sensitization.
  • 19. 5. FORMATION OF CORNIFIED ENVELOPE
  • 22. KERATINIZATION IN A NUTSHELL • Upward maturation of basal keratinocytes into cornified cells. • Along the way: -Cells lose their nuclei and cytoplasmic organelles -Cells become filled inside with KIF that are embedded in the matrix derived from keratohyaline granules. -The plasma membrane of the cells thickens and forms an envelope. -Lamellar granules discharges lipids that surround the intercellular
  • 23. REFERENCES 1. Rooks Textbook of Dermatology 2. Fitzpatrick’s Dermatology in General Medicine 3. Bolognia’s Dermatology 4. Moschella’s Dermatology 5. IADVL Textbook of Dermatology

Notas do Editor

  1. Lower 2 layers are the proliferative compartment (aka progenitor population) and contains stem cells. Maturation population / differentiated population is from S. basale to S. corneum
  2. KGF – Keratinocyte Growth Factor
  3. CK – Cytokeratin / Keratin KIF – Keratin intermediate Filaments
  4. CK – Cytokeratin / Keratin KIF – Keratin intermediate Filaments
  5. CK – Cytokeratin / Keratin KIF – Keratin intermediate Filaments
  6. ND – Not determined Arrhythmogenic right ventricular cardiomyopathy (ARVC) – previously referred to as arrhythmogenic right ventricular dysplasia (ARVD) SPPK - Striate palmoplantar keratoderma
  7. Periplakin, envoplakin