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2/7/2014

Epitelisasi

• Epitelialisassi :
– Pembentukan lapisan epitel baru di daerah luka
• Tujuan epitelialisasi
– Mencegah infeksi
– Minimalisasi kehilangan air/dehidrasi

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Stages in the Epithelialization of a


Simple Skin Wound
1. Retraction of the edges of the wound.
2. Rapid covering of the wound by an exudate or a blood clot.
3. Detachment of marginal epidermal cells from their underlying basal
lamina.
4. Mobilization of epithelial cells closest to the margins of the wound.
5. Migration of epidermal cells over a simple exudate or under a blood clot.
6. Cessation of migration when migrating epithelial cells from opposite
sides of the wound meet.
7. Initiation of mitotic activity in epidermal cells along the edge of the
wound.
8. Thickening of wound epithelium by further migration or mitotic activity
of the wound epithelium itself.
9. Re-formation of basal lamina and attachment of basal cells to it.
10. Final structural and functional remodeling.

Epithelization

1. sealed by clot formation

2. epithelial cell migration across the defect

3. keratinocytes – detatchment, migration,


proliferation, differentiation,
stratification

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Stages in the healing of a mammalian


skin wound
A) Epidermal growth factor (EGF) from the wound is one
of the factors that initiates mobilization of the wound
epidermis. AP-1, activator protein-1; EGFR, epidermal
growth factor receptor.

B) Growth factors from the clot stimulate not only


epidermal migration, but also angiogenesis and fi
broblast activation. Newly expressed integrins
facilitate adhesion of the migrating epidermal cells to
the substrate. Mitosis (asterisks) occurs in basal
keratinocytes near the wound margin. FGF, fi broblast
growth factor; PDGF, platelet-derived growth factor;
TGF, transforming growth factor; VEGF, vascular
endothelial growth factor.

Having digested their way through the clot, sheets of wound


epidermal cells migrate over extracellular matrix molecules and
meet near the center of the wound. The remains of the clot are
then shed.

Epithelialization
 Basal epithelial cells
at the wound margin
flatten (mobilize)
and migrate into the
open wound
 Basal cells at margin
multiply (mitosis) in
horizontal direction
 Basal cells behind
margin undergo
vertical growth
(differentiation)

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ROLE OF THE SUBSTRATE IN


REGENERATION

• relationship between the regenerating cells


and their substrate is critical for:
– maintenance of normal tissue functions and
– the migrations or changes in state that are part of
healing and regenerative processes
• cell adhesion molecules: membrane-bound
glycoprotein molecules that mediate
attachments between cells and other cells or
components of the ECM

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integrin

Matriks ekstrasel /ECM


• Macam-macam :
– Kolagen
– Proteoglikan
– Fibronektin, Laminin, dan protein lain dari ECM
• membran basal dan Jaringan ikat

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• ECM function:
– Mechanical support
– Differentiation
– Contain many active and inactive growth factors

Kolagen
• merupakan glikoprotein
• disintesis terutama oleh
fibroblast, sel otot polos
dan sel epitel
• ada 20 tipe kolagen
• struktur kolagen memiliki
kesamaan pada :
– semua molekul kolagen
memiliki trimer yang
terdiri dari rantai
polipeptida  rantai α
– 3 rantai polipeptida
kolagen berikatan
membentuk struktur
yang unik – rodlike triple
helix

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Sintesis kolagen

• Diawali dengan pembentukan prokolagen


• Propeptida pada prokolagen akan dipotong (di luar sel)
kolagen tersusun membentuk fibril kolagen
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ECM
collagen

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ECM: Non collagen


• Laminin

Laminin

• Terdiri dari 3 rantai


polipeptida yang berikatan
melalui rantai disulfida
• Berperan dalam migrasi sel,
diferensiasi, pertumbuhan
• Berperan dalam migrasi PGC
• ECM lain : tenascin, entactin,
trombospondin

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Proteoglikan
• Kompleks
protein
polisakarida
• Terdiri atas :
– core protein
berikatan
dengan rantai
glikosamino-
glikans
(GAG) 
terdiri atas disakarida yang berulang
• mengikat banyak molekul air
• membentuk gel yang porous

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Basal membran
• Mengelilingi sel otot dan sel lemak
• Di bawah jaringan epitel, sel-sel
endotelium
• tempat pelekatan sel;
• substrat untuk migrasi sel;
• membatasi jaringan dalam suatu
organ,
• sebagai suatu barier makromolekul.
BM mencegah lalunya protein dari
darah  pada dinding kapiler
Dalam ginjal double layer yang
memisahkan kapiler pada glomerulus
dari dinding tubulus ginjal.
• sebagai barier untuk invasi sel ke
suatu jaringan

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Cell-ECM interaction

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• EMT pathway

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