Extracellular Matrix Flashcards
What’s the function of extracellular matrix?
1) structure
2) defense and protection (barrier)
3) nutrition (diffusion of metabolic fuels)
4) diffusion of gases, molecules and ions
5) cell growth and survival
6) cell migration
7) lubrication
What are the three ECM constituents?
ground substance, fibers, and elastic
What is in the ground substance of ECM?
1) glycosaminoglycans (GAGs)
2) proteoglycans
3) water
4) adhesive glycoproteins
What are the fibers in ECM?
collagen, reticular (type III collagen), and elastic
What is the hallmark of tissue repair?
granulation tissue
How is granulation tissue characterized?
loose ECM with a lot of ground substance, very vascular, scattered collagen fibers, and edema from excess fluid. eventually formation of scar (dense collagenous tissue)
How does ECM drive the cell cycle?
more contact with ECM leads to an increased chance of cell division
Why does cell to cell contact inhibit cell division?
the contact between cells create a stable cellular environment (does not have contact with growth factors in ECM)
What is the another repair mechanism besides granulation tissue?
damaged cells are replaced by functionall cells if the ECM framework remains intact to structure cell growth. if ECM framework is lost, then granulation tissue repair is used
What happens to the hydrated state of tissue when there is excessive accumulation of glycosaminoglycans?
increases due to the negatively charged carboxyl groups (high affinity for water)
What are some glycosaminoglycans that exist in ECM?
1) dermatan sulfate
2) chondroitin sulfate
3) heparan sulfate
4) keratan sulfate
5) hyaluronic acid
6) heparin
Explain what could cause protrusion of the eyes in Grave’s disease.
increased deposition of glycosaminoglycans (chondroitin sulfate and hyaluronic acid) in retro-orbital space
What is syndecan?
transmembrane proteoglycan that is a co-receptor for fibroblast growth factor (FGF), aids in controlling proliferation and differentiation
What is perlecan?
proteglycan in the dermal-epidermal junction, capillaries, and hair follicle. also help with proliferation and differentiation
What happens when the gene for perlecan is inactivated?
defective skeletal development. without perlecan, skeletal tissue is unable to develop and this leads to severe skeletal deformation
Where is fibronectin found?
connective tissue, blood plasma, and embryonic tissue
Where is laminin found?
basal lamina
Where is entactin found?
basal lamina
Where is tenascin found?
embryonic tissue
Where is chondronectin found?
cartilage
Where is osteonectin found?
bone
What happens when we disrupt fibronectin?
cells cannot differentiate
What is the most abundant type of collagen?
type I
What is another name for type III collagen?
reticular
What type of collagen is found in dermis, tendon, bone, fibrocartilage, etc?
I
What type of collagen is found in hyaline an elastic cartilage?
II
What type of collagen is found in basal lamina?
IV
What type of collagen is found in dermis?
VII
What type of collagen is found in spleen, liver, lymph nodes, smooth muscle, skin and lungs?
III
What amino acid is measured to calculate the concentration of collagen?
hydroxyproline
What is the most abundant protein in the human body?
collagen
What are the two ways to turnover collagen?
proteolytic degradation and phagocytic degradation. lysosomal hydrolases play a big role in this
What’s the name of the cells that synthesize collagen?
fibroblasts
What stain can be used to detect reticular fibers (collagen type III)?
silver stains because reticular fibers are argyrophilic (silver loving), PAS positive as well
What staining techniques can be used to identify fibers and lamellae?
Resourcin-fuchsin and Verhoeff
What is the composition of elastic fiber?
proelastin (desmosine and isodesmosine)
microfibril-associated glycoprotein
fibrillin (I & II)
What disease is associated with defect in type III collagen? Symptoms: varicose veins, aortic rupture, and intestinal rupture
Ehlers-Danlos type IV
What disease is associated with defective hydroxylation of lysine? Symptoms: hyperelasticity of the skin, rupture of the eyeball
Ehlers-Danlos type VI
What disease is associated with defective type I collagen? Symptoms: joint dislocation and hypermobility of joints.
Ehlers-Danlos type VII
What disease is associated with decreased hydroxylation of proline caused by a deficiency in vitamin C? Symptoms: gum ulceration and hemorrhages
Scurvy
What disease is associated with defect in the synthesis of type I collagen? Symptoms: spontaneous fractures and cardiac insufficiency.
Osteogenesis imperfecta
What disease is associated with defective synthesis of elastic fibers? Symptoms: aortic aneurysm or rupture, myopia, detached lens, skeletal defects (long thin arms, legs, toes, and fingers), pectus excavatum (sternum caves in) and scoliosis
Marfan Syndrome
What is the basal lamina composed of?
lamina lucida and lamina densa
What is the basement membrane composed of?
basal lamina plus lamina fibroreticularis
What is the function of collagen VII in the basement membrane?
it serves to anchor the lamina densa and lamina fibroreticularis
What is fibroreticularis?
fibronectin and types I & III collagen
What staining technique can be used to identify membranous nephropathy?
silver methenamine stain
What adhesive glycoproteins can be found in basal lamina?
laminin and entactin
What adhesive glycoproteins can be found in embryonic tissue?
fibronectin and tenascin
What adhesive glycoproteins can be found in cartilage?
chondronectin
What adhesive glycoproteins can be found in bone?
osteonectin
What adhesive glycoproteins can be found in blood plasma?
fibronectin
What adhesive glycoproteins can be found in connective tissue?
fibronectin
What does fibronectin bind to?
integrins collagen heparin heparan sulfate hyaluronic acid
What does laminin bind to?
integrins
heparan sulfate
collagen (IV)
entactin
What does entactin bind to?
laminin
integrin
type IV collagen
What does tenascin bind to?
syndecans and fibronectin
What does chondronectin bind to?
collagen (II)
chondrotin sulfates
hyaluronic acid
integrins of chondrocytes
What does osteonectin bind to?
collagen (I)
proteoglycans
integrins of bone cells (osteocytes and osteoblasts)
Where will you find type I collagen?
dermis tendon bone dentin cementum fibrocatilage organ capsules
Where will you find type II collagen?
hyalin and elastic cartilage
Where will you find type III collagen?
spleen liver lymph nodes smooth muscle skin lung
Where will you find type IV collagen?
basal lamina
Where will you find type VII collagen?
dermis
