This is a powerpoint presentation on the epidermal keratinization and its associated disorders, presented by Dr. Jerriton, Dermatology resident of SVMCH, Pondicherry.

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

3. LAYERS OF EPIDERMIS

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)

9. STRUCTURE OF KERATIN

10. FORMATION OF KIF

11. DISTRIBUTION OF KIF

12. DISORDERS OF KERATIN

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.

14. STRUCTURE OF DESMOSOME

15. DISORDERS OF DESMOSOME

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.

17. FLIAGGRIN GENE MUTATION

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

21. CALCIUM PUMP DISORDERS

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