2. EPIDERMAL DIFFERENTIATION COMPLEX
• The cassette of genes present in 2 Mb region of long arm of Chromosome 1 which
encodes more than 25 genes responsible for epithelial tissue development & repair
by regulating the terminal differentiation of keratinocytes.
• It has role in structural integrity, signal transduction and cell cycle progression.
3. EDC
• These genes encode following proteins –
• Involucrin – Str. Corneum
• Loricrin
• SPR – Small Proline Rich proteins
• Intermediate filaments associated profilaggrin.
• Trichohyalin
• S100A proteins.
Str.
Granulosum
4. DIFFERENTIATION
• Epidermal cells detaches from the basal lamina & moves towards skin surface.
• During the movement, they undergo a terminal differentiation to form Stratum
Corneum.
• This involves the formation of proteins–
• Keratin - actin cytoskeletal proteins of corneocytes
• Filaggrin – structural monomer proteins.
5. • In addition it involves –
• Formation of cornified envelope,
• Changes in the expression of intracellular lipids,
• Membrane glycolipids,
• Growth factor receptors,
• Adhesion proteins,
• Blood group antigens.
6. FILAGGIRIN
• Filament aggregating protein.
• Histidine rich basic protein.
• It aggregates the keratin filaments into bundles inside corneocytes and forms a
lattice structure in lower layer in stratum corneum.
• Only expressed in cornified stratified epithelia not in areas like esophagus and
airways.
7. • It is formed by maturation of profilaggrin by various proteases present in the
keratinocytes of Str. Granulosum while entering Str. Corneum.
• In later stages of differentiation,
• keratin filaments bundled with filaggrin monomer to become cross-linked to the
cornified cell envelope.
8.
9. FILAGGRIN DEGRADATION
• During upward movement of corneocytes, intracellular filaggrin molecules are
degraded into many hygroscopic free amino acids like –
• Urocanic acid,
• Pyrolidone carboxylic acid, and their derivatives
• by proteases –
• Caspases 14
• Bleomycin hydrolase , etc.
• Defect in caspase 14 causes defect in degradation of filaggrin.
10. Defect in filaggrin –
• Deficiency or decrease in filaggrin reduce natural moisturizing tendency of skin.
• It result in barrier breakage of Str. Corneum.
• It may increases the chances of external allergen penetrating into the skin,
increases the risk of percutaneous sensitization against various allergens.
11. FUNCTIONS OF FILAGGRIN
By using various microscopy, based on the nature of filaggrin, Str. Corneum is divided into three
layers –
a) Lower layer – It provide physical strength and water impermeable layer due to the
presence of mature filaggrin and keratin intermediate filaments bundles.
b) Middle layer – It acts as a natural moisturizing layer and permeation barrier by holding
water in this layer by the presence of hygroscopic amino acids after degradation of
filaggrin.
c) Upper layer – It acts like a sponge , water comes in and out due to proteolytic degradation
of filaggrin.
12.
13. 2. KERATOHYALINE GRANULES
• These are cellular inclusions seen in Stratum Granulosum which disappears after
keratinocytes enter Stratum Corneum.
• It mainly composed of –
• Profilaggrin
• Keratin intermediate Filaments ( KF ),
• Loricrin.
• Profilaggrin – Precursor of filaggrin monomer.
• KF – Anchoring proteins.
14. • Loricrin –
• Present in keratohyaline granules in Str. Granulosum.
• Cysteine rich protein
• Forms the major protein component of cornified envelope
• >70% of cornified envelope mass.
• Its expression depends on intracellular calcium levels.
• Up-regulated by – High intracellular calcium levels.
• Down-regulated by – Retinoids.
15. 3. MEMBRANE COATING GRANULES
• They are also called – Lamellar granules or ODLAND BODIES
• They are granules present in upper part of Stratum Spinosum and in Stratum
Granulosum.
• They migrate towards periphery of the cells as they enters the granular layer.
• It contains –
• Phospholipids
• Glycolipids
• Free sterols
• These granules fuse with plasma membrane to discharge their content into intercellular
space forming an important barrier to permeability and inter cellular cohesion.
16. 4. CORNIFIED ENVELOPE
• A highly insoluble cell envelope in Stratum Corneum deep to plasma membrane.
• Precursors –
• Involucrin – preferred substrate for transglutaminase enzyme.
• SPR – Small Proline Rich proteins :
• Cornifin ( SPR 1 )
• Pancornulin.
• Membrane associated precursors :
• Envoplakin
• Periplakin
• 61 kDa Protein
17. Formation of envelope –
• Triggered by intracellular calcium.
• Transglutaminase enzymes cross link plakins and involucrin and other desmosomal
proteins forming a scaffold along the entire inner surface of plasma membrane –
forming envelope.
• These assembly results in durable , flexible dead cells ( corneocytes ) that have
mechanical and water permeability barrier functions.