Exam #1: ECM Flashcards
What are the molecular constituents of the ECM?
- Ground Substance
- Fibers
What are the different types of ground substance?
- Glycosaminoglycans
- Proteoglycans
- Water
- Adhesive glycoproteins
What are different fibers in the ECM?
- Collagen
- Reticular Fiber
- Elastic
Reticular Fiber
Type III Collagen
Granulation Tissue
- Replacing functional cells w/ ECM in response to injury
- Hallmark of tissue repair
- Loose, edematous, & vascular
Mature Scar
Loose granulation tissue replaced with dense collagenous tissue
How does the ECM drive the cell cycle?
- No contact w/ substrate= low probability of division
- Cell perched on adhesive patch= increases probability of division
- Cell spread on large adhesive patch= high probability of division
Focal Adhesions
Connection between cell & ECM that regulate:
- cell division
- growth
- survival
Injury to cell with intact matrix
Regeneration by functional cells
Injury to cell & matrix
Repair by granulation & scarring (non-functional cells)
What happens to the hydrated state of tissue when there is excessive accumulation of glycosaminoclycans?
Increase b/c of negatively charged carboxyl groups that attract water
What are the different glycosaminoglycans that exist in the ECM?
- Dermatin Sulfate
- Chondroitin Sulfate
- Heparan Sulfate
- Keratan Sulfate
- Hyaluronic Acid
- Heparin
Exopthalmous
- Grave’s Disease
- Autoantibodies to TSH
- Causes increased deposition of glycosaminoglycans in the retro-orbital space
- Specifically, Chondriotin Sulfate & HA
- Increases hydration state and pushes the eyes outward
Proteoglycan
- “Bottle-brush” appearance
- Core protein with Glycosaminoglycans attached
- Link with HA to form an aggrecan
Syndecan
- Transmembrane proteoglycan
- FGF receptors adjacent
- Co-receptor for FGF receptor
- Attached by Heparan Sulfate
Perlecan
- Dark brown in appearance
- Found in the interface between epidermis & dermis
- Surrounds blood vessels
- Plays a role in the development of skeletal tissue
Perlecan- Null
Defective skeletal development
What are the three typical binding domains of a multiadhesive glycoprotein?
1) Cell adhesion molecule aka CAM e.g. Integrin
2) Collagen fibers
3) Proteoglycans
What are the six types of adhesive glycoproteins?
1) Fibronectin
2) Laminin
3) Entactin
4) Tenascin
5) Chondronectin
6) Osteonectin
Laminin
Adhesive Glycoprotein in Basal Lamina
Entactin
Adhesive Glycoprotein in Basal Lamina
Tenascin
Adhesive Glycoprotein in Embryonic Tissue
Chondronectin
Adhesive Glycoprotein in Cartilage
Osteonectin
Adhesive Glycoprotein in Bone
What is the role of Fibronectin in development?
- Normal development of salivary glands
- When blocked, glands do not differentiate
Laminin
Binding domains:
- Dystroglycan (cell-adhesion molecule)
- Collagen
- Heparan Sulfate (proteoglycan)
Plasma membrane of muscle
What is the most abundant fiber type seen in the ECM?
Collagen
Type I Collagen
- Most abundant
- Associated with tendons, ligaments, fibrocartilage, cementum, dentin, bone, dermis, & any organ w/ a connective tissue capsule
- Acidophillic (pink)
Type II Collagen
- Hyaline & Elastic Cartilage
Type III Collagen
- Reticular Cartilage
- Spleen, liver, lymph nodes, smooth muscle, skin, lung
- Forms a “delicate network” for cells
- Argyrophilic (silver loving)
- PAS positive (carbohydrates associated)
Type IV Collagen
Basal Lamina
Type VII Collagen
- Dermis
- Connects the basal lamina with the underlying dermis
What amino acid is measured to calculate the concentration of collagen?
Hydroxyproline
How is collagen turned over?
- Proteolytic Degradation
- Phagocytic Degradation
What do cardiac muscle cells appear in response to a remote MI?
- Blue from collagen deposition (granulation first)
- Trichome method of staining
Keloid
Excessive accumulation of collagen/ excessive scar formation
What are Elastic Fibers composed of?
- Proelastin
- Microfibril-associated glycoprotein
- Fibrillin 1&2
What are unique amino acids to elastic fibers?
Desmosine & Isodesmosine
Ehler’s Danlos Type IV
- Type III Collagen (Reticular Fibers)
- Varicose veins, aortic rupture, intestinal rupture
Ehler’s Danlos Type VI
- Defective Hydroxylation of Lysine
- Hyperelasticity of the skin, rupture of the eyeball
Ehler’s Danlos Type VII
- Type I Collagen
- Joint dislocation & hypermobility
Marfan’s Syndrome
- Defective synthesis of elastic fibers
- Aortic aneurysm, skeletal defects, pectus excavatum, scoliosis
Basal Lamina
- Interface between epithelial cells & extracellular components/ underlying connective tissue
- Found in epithelium, kidney glomerulus, & muscle cell
Basement Membrane
- Basal Lamina ( Lamina lucida & Lamina densa)
- PLUS Lamina fibroreticularis
Lamina Lucida
- Laminin
- Entactin
- Integrins
- Dystroglycans
Lamina Densa
- Type IV Collagen
- Fibronectin
- Perlecan
Lamina Fibroreticularis
- Fibronectin
- Type I Collagen
- Type III Collagen
What anchors the Lamina Densa to the Fibroreticularis?
Type VII Collagen
Membranous Nephropathy
- Autoantibodies produced against antigens
- Deposit in the basal lamina of the glomerulus
- Compliment is activated
- Leads to a degradation of the wall of the vasculature
