Tugas Pembacaan ECM_textbook of histology.pptx

Tugas pembacaan

1. Andi Sri Utari C075231005 Dosen Penanggung Jawab dr. Muh . Husni Cangara , Ph.D , Sp.PA (K) Dosen Pendamping dr. Haslindah Dahlan, Sp.PA DEPARTEMEN PATOLOGI ANATOMIK FAKULTAS KEDOKTERAN UNIVERSITAS HASANUDDIN CHAPTER 4 EXTRACELLULAR MATRIX TEXTBOOK OF HISTOLOGY (p.81- 97)

2. Visi Misi Program Studi Patologi Anatomi Fakultas Kedokteran Universitas Hasanuddin VISI Menjadi program studi yang unggul bertaraf internasional dalam bidang akademik , riset , publikasi , pengabdian masyarakat dan menghasilkan dokter spesialis Patologi Anatomi yang professional, berdaya saing tinggi dan menghayati nilai-nilai etika , agama, dan kemanusiaan MISI Mengembangkan sistem pendidikan belajar sepanjang hayat (long life learning) yang unggul dan berbasis kompetensi dalam domain kognitif , afektif , dan psikomotor {MISI PENDIDIKAN} Menyelenggarakan penelitian dan menerbitkan publikasi yang bertaraf nasional maupun internasional {MISI RISET} Menyelenggarakan pengabdian masyarakat yang relevan dengan kebutuhan masyarakat (MISI PENGABDIAN MASYARAKAT} Mengadakan dan mengembangkan sumber daya manusia pendidik dan kependidikan dalam hal jumlah dari mutu sesuai kebutuhan program studi (MISI KETENAGAAN) Menyelengarakan kegiatan yang bersifat kesejawatan dan pengembangan profesionalisme berkelanjutan (MISI ALUMNI)

3. INTRODUCTION Cells of multicellular organisms congregate to form structural and functional associations, known as TISSUES . Each of the four basic tissues of the body epithelium, connective tissue, muscle, and nervous tissue All tissues are composed of cells and an extracellular matrix (ECM) , a complex of nonliving macromolecules manufactured by the cells and exported by them into the extracellular space, that is, the space between cells

4. EXTRACELLULAR MATRIX ( ECM ) The ECM of connective tissue proper, the most common connective tissue of the body, is composed of a hydrated gel-like ground substance with fibers embedded in it

5. GROUND SUBSTANCE Glycosaminoglycans ( GAGs ), Proteoglycans , Cell Adhesive Glycoproteins.

6. GROUND SUBSTANCE Glycosaminoglycans ( GAGs ), GAGs are negatively charged, long, rod-like chains of repeating disaccharides that have the capability of binding large quantities of water The sulfated GAGs include keratan sulfate , heparan sulfate , heparin, chondroitin 4-sulfate, chondroitin 6-sulfate, and dermatan sulfate . The only nonsulfated GAG is hyaluronic acid (hyaluronan),

7. GROUND SUBSTANCE Proteoglycans When sulfated GAGs form covalent bonds with a protein core, they form a family of macromolecules known as proteoglycans These large structures look like a bottle brush, with the protein core resembling the wire stem and the various sulfated GAGs projecting from its surface in three-dimensional space, as do the bristles of the brush

8. GROUND SUBSTANCE Glycoproteins (Cell Adhesive Glycoproteins) The ability of cells to adhere to components of the ECM is mediated to a great extent by cell adhesive glycoproteins. The major types of adhesive glycoproteins are fibronectin, laminin, entactin, tenascin, chondronectin , and osteonectin .

9. Fibronectin is a large dimer composed of two similar polypeptide subunits, each about 220,000 Da, attached to one another at their carboxyl ends by disulfide bonds The region of the fibronectin that is specific for adhering to the fibronectin receptors has the three-residue sequence arginine, glycine, and aspartate Fibronectin is produced mainly by connective tissue cells known as Fibroblasts. Fibronectin is also present in blood as plasma fibronectin, where it facilitates wound healing, phagocytosis, and coagulation Fibronectin

10. Laminin is a very large glycoprotein (950,000 Da) composed of three large polypeptide chains, A, B1, and B2 The location of laminin is almost strictly limited to the basal lamina; therefore, this glycoprotein has binding sites for heparan sulfate, type IV collagen, entactin, and the cell membrane Laminin Entactin Entactin (also known as nidogen and is about 150,000 Da) binds to the laminin molecule where the three short arms of that molecule meet each other. Entactin also binds to type IV collagen, thus facilitating the binding of laminin to the collagen meshwork.

11. Tenascin is a large glycoprotein (250,000 to 300,000 Da) composed of six polypeptide chains held together by disulfide bonds Tenascin’s distribution is usually limited to embryonic tissue, where it marks migratory pathways for specific cells. Tenascin Chondronectin and Osteonectin (about 40,000 Da) are similar to fibronectin. The former has binding sites for type II collagen, chondroitin sulfates , hyaluronic acid, and integrins of chondroblasts and chondrocytes. Osteonectin possesses domains for type I collagen, proteoglycans, and integrins of osteoblasts and osteocytes. In addition, it may facilitate the binding of calcium hydroxyapatite crystals to type I collagen in bone Chondronectin and Osteonectin

12. F IBERS The fibers of the ECM provide tensile strength and elasticity to this substance . Three types of fibers on the basis of their morphology and reactivity with histological stains: Collagen, Reticular, and Elastic

13. A. Collagen Fibers: Structure and Function This family of proteins is very abundant, constituting about 20% to 25% of all the proteins in the body Collagens are classified into four categories: Fibril-Forming, Fibril-Associated, Network-Forming, and Transmembrane Collagens F IBERS

14. Fibril-Forming Collagen Fibril-Forming Collagen , as its classification implies, forms flexible fibers whose tensile strength is greater than that of stainless steel of comparable diameter.

15. Fibril-Associated Collagens Fibril-Associated Collagens have been recognized as stabilizing collagens because they form molecular bridges between fibril-forming collagens and components of the ground substance There are two types of fibril-associated collagens: • Type XII collagen that binds to type I collagen of the dermis of the skin and connective tissues of the placenta • Type IX collagen that binds to type II collagens of cartilage

16. Network-Forming Collagens Network-Forming Collagens are formed by epithelial cells and, unlike fibrous collagen types, are not exposed to procollagen peptidase, the enzyme that cleaves the telopeptides off the ends of the procollagen molecules There are two types of network-forming collagens: • Type IV collagen that forms the sheet-like lamina densa of the basal lamina • Type VII collagen that aggregates in sheaves to form anchoring fibers whose function is to attach the basal lamina to the lamina reticularis of the basement membran

17. Transmembrane collagens Transmembrane collagens (also known as collagen-like proteins) are integral proteins one of which, type XVII, functions in the adherence of the epidermis to the dermis. As such, these transmembrane collagens are components of the hemidesmosomes. There are three other types of transmembrane collagens, Types XIII, XXIII, and XXV (whose functions are not as yet understood)

18. Collagen Synthesis The synthesis of collagen occurs on the RER as individual Preprocollagen Chain which are α-chains possessing additional amino acid sequences, known as propeptides , at both the amino and carboxyl ends. It enters the cisterna of the RER, where it is modified. Preprocollagen molecules align with each other and assemble to form a tight helical configuration known as a Procollagen Molecule

19. Collagen Synthesis The newly formed molecule is shorter (280 nm in length) and is known as a Tropocollagen (collagen) molecule. Tropocollagen molecules spontaneously self-assemble, in specific headto -tail direction, into a regularly staggered array, fashioning fibrils that display a 67-nm banding representative of collagen types I, II, III, V, and X

20. B. Elastic Fibers Elastic Fibers , unlike collagen, are highly accommodating and may be stretched one and a half times their resting length without breaking. When the force is released, elastic fibers return to their resting length They are composed of Elastin, Fibrillin-1 and Fibulin-5 , and Type VIII Collagen F IBERS

21. Elastic Fibers Elastin is a protein that is rich in glycine, lysine, alanine, valine, and proline but has no hydroxylysine. Elastin is derived from a soluble protein precursor, Tropoelastin

22. Elastic Fibers The core of elastic fibers is composed of elastin and is surrounded by a sheath of microfibrils ; each microfibril is about 10 nm in diameter and is composed of the Glycoprotein Fibrillin-1

23. Integrin molecules of cells that synthesize elastic fibers bind to Fibulin-5 , a protein that has an affinity to itself as well as to tropoelastin and fibrillin-1. Type VIII collagen has also been demonstrated to form a part of elastic fibers. Because collagen is inelastic, it is believed that type VIII collagen acts to limit the amount of stretching that elastic fibers are permitted to undergo Elastic Fibers

24. BASEMENT MEMBRANE The basement membrane seen with light microscopy is shown by electron microscopy to be composed of The Basal Lamina and Lamina Reticularis

25. BASEMENT MEMBRANE Basal Lamina The basal lamina manufactured by the epithelium is composed of the lamina lucida and the lamina densa

26. BASEMENT MEMBRANE Lamina Reticularis The lamina reticularis , a region of varying thickness (usually about 200 nm), is manufactured by fibroblasts and is composed of types III, VII (anchoring fibrils), and XVIII and a slight amount of type I collagen; additionally, a slight amount of microfibrils is also present.

27. PATHOLOGICAL CONSIDERATIONS

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