Epitelisasi Epitelialisassi : Pembentukan lapisan epitel baru di daerah luka Tujuan epitelialisasi Mencegah infeksi Minimalisasi kehilangan air/dehidrasi 1
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 2
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) 3
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 4
integrin Matriks ekstrasel /ECM Macam-macam : Kolagen Proteoglikan Fibronektin, Laminin, dan protein lain dari ECM membran basal dan Jaringan ikat 10 5
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 12 6
Sintesis kolagen Diawali dengan pembentukan prokolagen Propeptida pada prokolagen akan dipotong (di luar sel) kolagen tersusun membentuk fibril kolagen 13 collagen ECM 7
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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 18 9
Proteoglikan Kompleks protein polisakarida Terdiri atas : core protein berikatan dengan rantai glikosaminoglikans (GAG) terdiri atas disakarida yang berulang mengikat banyak molekul air membentuk gel yang porous 19 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 20 10
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Cell-ECM interaction 12
EMT pathway 13