ECM Flashcards
What are the three basic ground elements of the ECM?
Ground substance
Fibers
Granulation tissues
What are the characteristics of the ground substance of the ECM?
amorphous, tranparent, colorless, and homogenous
What are the functional attributes of the ECM?
Structure Defense Nutrition Diffusion of gases, molecules, ions Cell growth, survival Cell migration Lubrication
Where is lubrication used?
cartilage (joints)
What does the ground substance include?
GAGs (= mucopolysaccharides)
Proteoglycans
Water
Adhesive glyoproteins
What are the constituents of the fibers?
Collagen
Reticular (type III collagen)
Elastic
What are the two type of cell repair?
Granulation tissue (replacing dead cellswith ECM) (scar)
Replace functional tissue
How does the ECM drive the cell cycle?
Senses points of contact, such that more contacts will increase prb of growth
What is the probability of a cell suspended in agar of entering S phase?
8%
What determines if a tissue will replace damage with scar tissue or cells?
Whether or not the ECM is damaged–if it is not, then replace with cells.
What causes the attraction of water to GAGs?
Carboxyl groups
What are the six types of GAGs?
Dermatan sulfate Chondrotin sulfate Heparan sulfate Keratan sulfate Hyaluronic acid Heparin
What causes the increased hydration of tissue behind the eyes in grave’s disease?
Chrondroitin sulfate and hyaluronic acid deposition
What is the structure of proteoglycans?
Thistle brush
What is the backbone of proteoglycans? Branches?
Hyluronic acid
GAGs are branches
What is syndecan?
Transmembrane proteoglycan that connects FGF receptors via GAG branches (coreceptor for fibroblast growth factor)
What is perlecan?
Proteoglycan present in the basement membrane of tissues involved in proliferation, differentiation etc.
Inactivation of perlecan results in what?
Skeletal dysplasia
What are the 3 typical binding domains for multiadhesie glycoproteins?
cell adhesion molecules (CAMs, e.g. integrin)
Collagen fibers
Proteoglycans
Over hydration of the ground substance leads to what?
Edema
The ground substance fill space between what and what?
Cells and fibers
What are proteoglycans?
Linear chains of glycosaminoglycans bound to a protein core form proteoglycans
What percent of the molecular weight of a proteoglycan is due to carbs?
80-90%
What are glycosaminoglycans?
Long chains of unbranched poly saccharides consisting of a repeating disaccharide unit
What is the substance that forms the “core” of the proteoglycans?
Hyaluronic acid
What are the function of perlecans?
Cell adhesion Cell proliferation Cell differentiation Glomerular filtration Development Growth factor binding
What is the probability of a cell dividing when it is perched on a small adhesive patch?
30%
What is the probability of a cell dividing when it is perched on a LARGE adhesive patch?
90%
When GAGs form a bond with Hyluronic acid, what does it then become?
Aggregans
What is a major consequence of aggregan formation?
Increases hydration state
What are aggregans attached to?
Type I collagen
What are multiadhesive glycoproteins?
are glycoproteins that molecularly tether the cell to extracellular elements
What are the three primary binding sites for multiadhesive glycoproteins?
one for integrins (cell adhesion molecules), one for collagen fibers, and one for proteoglycans
What is the binding domain and location of fibronectin?
BInds to integrins, collagen, heparin, heparan sulfate, hyaluronic acid
Location = connective tissue, blood plasma, and embryonic tissue
What is the binding domain and location of Laminin?
Binds to integrins, heparane sulfate, collagen IV, and entactin
Found in the basal lamina
What is the binding domain and location of Tenascin?
Binds to syndecans and fibronein
Location = basal lamina
What is the binding domain and location of chondronectin?
Binds to collagen, II, chondroitin sulfates, hyaluronic acid, integrins of chondrocytes
Location = carilage
What is the binding domain and location of osteonectin?
Binds to collagen, proteoglycans, and integrins of bone cells
Location = bones
Blocking fibronectin blocks what important development process in mice?
mophogenesis
What is the most abundant protein in the body?
Collagen (20-25% of all protein)
What are the three major amino acids that make up collagen?
Glycine, hydroxyproline, hydroxylysine
Where is type I collagen found?
Dermis, tendon, bone, dentin, cementum, fibrocartilage, organ capsules
Where is type II collagen found?
Hyaline and elastic cartilage
Where is type III collagen found?
Spleen, liver, lymph nodes, smooth muscle, skin, lung
Where it type IV collagen found?
Basal lamina
Where is collagen I synthesized?
Fibroblasts, odontoblasts, cementoblasts, osteoblats, chondroblasts
Where is collagen II synthesized?
Condroblasts
Where is collagen III synthesized?
Smootuh muscle cells, fibroblasts, reticular cells
Where is collagen IV synthesized?
Endothelial cells, epithelial cells, schwann cells, smooth muscle cells
What is the function of type I collagen?
Resists tension
What is the function of type II collagen?
resistes pressure
What is the function of type III collagen?
maintains structure in expansible organs
What is the function of type IV collagen?
Supports delicate structures
Filtration
what is the molecular organization of type I collagen?
Fibril-forming collagen leading to the formation of fibers
what is the molecular organization of type II collagen?
Fibril-forming collagen
what is the molecular organization of type III collagen?
Fibril-forming collagen leading to the formation of fibers
what is the molecular organization of type IV collagen?
Network-forming collagen
Where is type VII collagen found?
Dermis
What types of cells synthesize type VII collagen?
epidermal cells
What is the function of type VII collagen?
anchors the lamina densa to the lamina reticularis
What is the molecular organization of type VII collagen?
Anchoring collagen
What amino acid is measured to calculate the [C] of collagen?
Hydroxyproline
Is collagen acidophilic or basophilic?
Acidophilic
What are the two means collagen can be degraded?
Proteolytic
Phagocytic
Trichrome methods will color collagen what color?
Blue
Reticular fibers are composed of what?
Type III collagen
What do reticular fibers stain with?
Argyrophilic (silver) and PAS
What types of cells synthesize retiular fibers?
fibrocytes, reticulocytes, smooth myocytes, and schwann cells
True or false: reticular fibers branch?
True
What is the function of elastic fibers?
Imparts tissue with elasticity
Which stain would you use to highlight elastic fibers?
Verhoeff or resorcin-fushsin
How are elastic fibers arranged?
b. Densely arranged in bundles (ligamentum flavum)
What are the three components of elastic fibers?
Proelastin (contains a.a. desmosine and isodesmosine)
Microfibril-associated glycoproteins
Fibrillin (1 and 2)
Which amino acids are unique to the ECM?
Desmosine and isodesmosine
What is the defect and clinical relevance of Ehlers-Danlos type 4?
Mutation in the COL3A1 gene encoding type III collagen (reticular fibers)
Varicose veins, aortic rupture, intestinal rupture
What is the defect and clinical relevance of Ehlers-Danlos type 6?
Defective hydroxylation of lysine thereby destabilizing the strength of the collagen
Hyperelasticity of the skin, rupture of the eyeball
What is the defect and clinical relevance of Ehlers-Danlos type 7?
Mutations in the COL1A1 and COL1A2 genes encoding type I collagen
Joint dislocation and hypermobility of joints
What is the defect and clinical relevance of osteogenesis imperfecta?
Mutations in COL1A1 lead to a reduction in the synthesis of type I collagen
Spontaneous fractures and cardiac insufficiency
What is the defect and clinical relevance of strickler syndrome?
Mutation in COL2A1 gene encoding for type II collagen
Myopia, hypoplasia of mandible, arthritis
What is the defect and clinical relevance of Marfan syndrome?
Mutation of the fibrillin 1 gene located on chromosome 15
Aortic aneurysm or rupture, myopia, detached lens, skeletal defects (long, thin arms, legs, toes, and fingers; pectus excavatum; scoliosis
What is the defect and clinical relevance of scurvy?
Tropocollagen molecules cannot aggregate into fibrils due to decreased hydroxylation of proline caused by a deficiency in vitamin C
Gum ulceration and hemorrhages
Where is the basal lamina found?
Epithelium
Kidney glomerulus
Muscle cells
What are the components of the basal lamina?
Lamina lucida
Lamina densa
What is the composition of lamina lucida?
Laminin, entactin, integrins, dystroglycans
What is the composition of the lamina densa?
Type IV collagen, fibronectin, and perlecan
What are the components of the basemen membrane?
Basal lamina + lamina fibronreticularis
What is the composition of the lamina fibroreticularis?
Fibronectin and types I and III collagen
What type of collagen serves to anchor the lamina densa and lamina fibroreticularis?
VII
How does membranous nephropathy come about?
Anitbodies attacking the basement membrane of the kidneys
Observing a sample of kidney cells stained with silver methenamine through a light microcope, you see small, black projections coming off of the cells. What is your diagnosis?
Membranous nephropathy