Connective Tissue and Extracellular Matrix Flashcards
What is the ECM?
Large portion of tissue volume, in some cases most of volume
Made up of: collagen, elastin, the glycosaminoglycans (GAGs), and proteoglycans
GAGs = Hyaluronic acid and Heparan sulphate
What is collagen?
25% of all protein and major ECM protein
Rope like structures that RESIST TENSION, NOT COMPRESSION
What is the structure / assembly of collagen fibres?
Self assembly of preformed units
- Three chains make up procollagen peptidase = triple helix collagen molecules
- These assemble after secretion from ER into a collagen fibril which then make up collagen fibres
What is oral submucosal fibrosis?
The chronic consumption of the areca nut which contains a toxi compound called arecoline
Causes collagen deposition, inhibiting tension and making it difficult to move mouth for eating / talking etc
Symptoms = presence of fibrotic bands and blanching or oral mucosa and inflammation, oral rigidity
What is elastin?
Like a rubber band x 5
Similar to collagen but assemble from hydrophobic uncoiling domains
Relaxed = curled state Tense = stretched / straightened
What are the characteristics of glycosaminoglycans (GAGs)?
Long, unbranched polysaccharides made from repeating disaccharide units (amino sugar and uronic acid)
Strong negative charge
Attracts and traps water using strong charge (water = polar) as well as trapping other cations (sodium, potassium, and calcium)
GAGs provide hydration and swelling pressure to withstand compression forces
What are the characteristics of the GAG hyaluronic acid?
Formed at cell surface by enzyme complex
Extremely long chains that aren’t sulphated
The scaffold binding many proteoglycans (goo molecule)
Major component of ECM, especially abundant in synovial fluid
What are the characteristics of the GAG heparan sulphate?
Components manufactured in golgi
Similar to hyaluronic acid, except highly sulphated
Regulates a wide range of biological activities including angiogenesis, blood coagulatin, and cellular signalling
What are proteoglycans?
Protein core with attached GAGs, known as the filler of ECM space
The major biological function of proteoglycans derives from the physicochemical characteristics of GAGs
Cells need to be bound to ECM, they need to stay static. How is this achieved?
Adhesion molecules aka hemidesmosomes etc
Why is the ECM in constant turn over?
It permits remodelling / adaptation to function
Synthesis balanced by degradation
Degradation occurs from enzymes (Hyaluronidase, proteinases, metalloproteinases (MMPs), and serine proteinases)
What makes healthy tissue?
TIMP / MMP is balanced
More TIMP = fibrosis
More MMP = degeneration metastasis (cancer induces lots of MMP)
What are the characteristics of matrix metalloproteinases?
Work to degrade both matrix and non-matrix proteins
Dependent on metals as cofactors (zinc, calcium, and magnesium)
Usually secreted in pro-enzymes form (inactive)
Activated by proteinases (serine) or reactive oxygen species (ROS)
Inhibited by tissue inhibitors of metalloproteinases (TIMPs)
What are the characteristics of serine proteinases?
Often activated by other serine proteinases
Not dependent on metals
Inhibited by serpins (plasminogen, plasminogen activators, trypsin, many clotting and inflammatory proteinases)
What are key characteristics to remember about conenctive tissue?
Usually have blood vessels (epithelium never has blood vessels inside of it)
Cells are separated from each other (fibroblasts, adipcosytes, mast cells)
Extracellular matrix (collagen, elastin, glycosaminoglycan, hyaluronic acid)
Support epithelium, organs, and other special tissues
