Extracellular matrix Flashcards
What are the functions of the extracellular matrix?
Cellular division Motility Differentiation Adhesion Structure
What secretes the extracellular matrix?
Cell secretes macromolecules for ECM
What are the main components of ECM?
Structural proteins (Collagen, Elastin)
Proteoglycans (protein-polysaccharides)
Adhesive Glycoproteins (Fibronectins, Laminins)
What is the purpose for collagens & elastins in the ECM
Provide strength & flexibility
What is the purpose for proteoglycans in the ECM?
Provide matrix for collagens and elastins to embed within
What is the purpose of Adhesive glycoproteins in ECM?
Attach cells to matrix
How much of total body protein is collagen?
25-30%
Polypeptides of collagen
Triple helix of glycine, hydroxylysine, hydroxyproline
How much weight can collagen hold?
1mm fiber = 20 lbs
How many different collagen genes are there?
25 different alpha chains
What provides collagen with it’s strength?
Cross-linked collagen bundles
What causes loss of joint function during aging?
Abnormal collagen cross-linking
What is the symptom of collagen synthesis deficiency?
Hypermobility of joints
What is elastin made of?
Proteins with Glycine & Proline with no hydroxylation
Elastin is crosslinked between lysines
What causes wrinkles and inflexible joints?
Loss of elastin with aging
What is Supravalvular aortic stenosis? (SVAS)
Mutations in elastin gene disrupt elastin synthesis and result in narrowing of aorta or pulmonary vessels
WHat are proteoglycans?
Glycoproteins with glycosaminoglycans
What are the glycosaminoglycan side chains?
Chondroitin sulfate
Keratan Sulfate
Heparin
What is the purpose for glycosaminoglycans?
Receptors, filtration, shock absorption, water retenetion
What is hyaluronate?
Proteoglycan that acts as backbone in collagen
What is the function of hyaluronate?
Lubricates any place with friction
What is Heparin/Heparan SUlfate?
Heparan Sulfate is found in every cell body, role in inflammation
Heparin is an anticoaglant
WHat is fibronectin?
Most common adhesive glycoprotein
Can be soluble, insoluble or partially soluble depending on splicing
What is the main function for fibronectin?
Maintains cell shape
Blood clotting (soluble form)
Guides immune cells to wound
What role does fibronectin play in cancer?
Carinomas are unable to synthesize fibronectin and cells lose their shape and detach from ECM
Giving fibronectin revert cells to normal shape and cells are no longer malignant
Where are laminins located?
Basal laminae under epithelial cells in muscle, fat and schwann cells
Separates ECM from epithelial cells
What is the function of the basal lamina?
Structural support
Selective permeability barrier
Why is the basal lamina important in cancer?
May allow the migration of cancer cells
What does disorded extracellular matrix remodeling lead to?
Scar formation
What tissues does the ECM provide a structural matrix for
All tissues
Bone & Cartilage specifically
Why is remodeling constant in the ECM?
Allows cells to be responsive to needs of the animal
What sites and cells is the ECm most active?
Cartilage (Chondrocytes)
Bone (Osteocytes)
Tendon (fibrocytes)
Crnea (Fibrocytes)
What are the parent cells of ECM and how do they regulate ECM?
Osteoblasts
Chondrocyte
Fibrocytes
Transcriptional regulation
What do ECM cells respond to?
Paracrine signaling (Growth factors)
Physical signaling from other cells/ECM
How is ECM degraded?
Metallproteinase enzymes
Serine proteases
What are the characteristics of metalloproteinase?
Requires zinc or calcium
Specific for 1 ECM compoenent
Are degradation enzymes auto-upregulated?
Yes, in pathways with a high turnover of ECM
What are the Tissue Inhibitors of metalloproteinase?
TIMP 1,2,3,4
Irreversibly bind to metalloproteinase
What are the Serine Protease inhibitors?
Alpha 1-antrypsin
What is Alpha 1-antrypsin deficiency?
A lack of Alpha 1-antrypsin serine protease inhibitor leads to excessive degradation of elastin by the neutrophil elastase enzyme
What diseases are caused by alpha 1-antrypsin deficiency?
Emphysema, COPD, cirrhosis
Treatment of alpha 1-antrypsin deficiency?
Intravenous infusions of alpha 1-antrypsin
What is panniculitis?
Alpha 1-antrypsin deficiency in dogs can cause hardening of the skin in to painful, hard lumps and patches
Can occur in a range of severity and age
