Extracellular Matrix and Wound Healing Flashcards
Integrins
- consists of a heterodimer between an alpha and beta integrin
- glycoprotein
- anchor the ECM to the cell membrane and the cytoskeleton
- are receptors that have ligands on either side of the cell membrane, and those ligands may be adaptor proteins
- many mutations in integrin genes are lethal
actin-linked cell-matrix junction
uses integrins to anchor actin filaments in cell to extracellular matrix
hemidesmosome
uses integrins to anchor intermediate filaments in a cell to extracellular matrix
epithelial tissue cells
connected by cell-cell junctions and have a limited ECM
- ECM is the basal lamina/basement membrane
- usually “outer” layer like skin
fibroblasts
secrete extracellular matrix
lamins
- heterotrimer: alpha, beta, and gamma subunits
- glycoprotein
- stay near the cell membrane and help cells stick together
- helps organize basal membrane
- helps with adhesion and migration of cells
collagen
- makes up majority of ECM
- triple helix = fibril
- glycoprotein
- can form sheets
- can cross the cell membrane
- can be protein part of proteoglycans
- can be associated with fibrils (hanging off other fibers)
- I and III that form fibers are most prevalent in cell
ehlers danlos syndrome
- associated with collagen I and V
- hypermobility
- elastic but fragile skin: easily torn and may scar easily
alport syndrome
- associated with collagen IV (basal lamina)
- progressive kidney failure: decreased filtering function of glomeruli
- hearing loss: can hear but message isn’t transmitted to brain
- eye deformities: lens shape or retina color can change but no loss of function
proteoglycans
- sugar-modified peptides (more sugar than protein)
- very big
decorin
- type of proteoglycan
- interacts with and regulates collagen fibers
versican
- type of proteoglycan
- interact with elastins and influences cell migration
- important in wound healing
aggrecan
- type of proteoglycan
- found in cartilage
syndecans
- only transmembrane proteoglycan
- intracellular domain interacts with actin (actin-linked cell matrix junction)
hyaluronan (HA)
- sugar that is on the proteoglycans
- only a sugar, but can interact with other proteins
- very hydrophilic, like to interact with water
- take up a lot of space
elastins
- flexible but remember their original shape
- composed primarily of hydrophobic amino acids
- cross-linked at lysine residues
- not glycosylated (strange for secreted protein)
- major ECM component of arteries
fibronectins
- hold other ECM components together and binds cell surface receptors
- multiple binding domains
- one gene for fibronectin but alternative splicing allows variation
- glycoprotein
- scaffolding function is important in wound healing
matrix metalloproteinases (MMPs)
- function to remodel ECM
- require Ca++ or Zn++ to work
- each ECM component has its own special MMP to degrade it
- MMPs are turned off (by Tissue inhibitors of MMPs- TIMPs) during wound healing by competitive inhibition
what tissues don’t form scars
fetal and oral wounds
vasculature in scars
fetal/ora: normal
normal scar: decreased
hypertrophic: decreased
keloid: increased
fibroblasts in scars
fetal/oral: regenerative
normal: myofibroblasts
hypertrophic: increased myofibroblasts
keloid: more increased
immune cells: inflamm response in scars
fetal/oral: decreased
normal: normal
hypertrophic: increased
keloid: more increased
collagen in scars:
fetal/oral: parallel; basketweave
normal: parallel and crosslinked
hypertrophic: parallel-ish and thinner fibrils
keloid: disordered and thicker fibrils
