wound healing and tissue repair I - lecture notes - julia Flashcards
what is the end result of wound healing and tissue repair?
formation of a collagenous scar
what is compensatory hypertrophy? in what organs does it take place?
when stable tissues regenerate after a portion has been removed in liver and kidney (so if you remove half of a liver, it’ll grow back)
what is the difference in the end result of healing between a wound and chronic inflammation?
- wounds result in scar formation
- chronic inflammation results in fibrosis
what is the functional ability of scar tissue?
nonfunctional except for holding tissue together
what is fibrosis?
diffuse scaring in the organ due to chronic inflammation
what is the difference between when regeneration and healing occur (ie what situations are required for each process)?
- regeneration requires intact tissue scaffolding (basement membranes especially)
- healing occurs when the tissue scaffolding has been altered or destroyed
what is the difference between the what is formed in the regeneration versus healing processes?
- in regeneration, new cells in tissue/organ are derived from division of stabile cells or new cells from stem cells
- healing involves combination of creation of new tissue cells and collagen deposition (fibrosis/scaring)
what is the difference between the ability of regeneration and healing to return tissues to their normal state?
in regeneration, normal state is reestablished, whereas in healing, totally normal state is never reestablished
what determines the degree of dysfunction an organ that has undergone healing will exhibit?
the amount of collagen that is deposited in the healing process
what is the consequence of chronic ischemic heart disease?
scaring
- collagen placed between myocardial cells
- eventually heart barely functional because there’s so much collagen diffusely present
what regulates cell proliferation (list)?
1: hormonal influences
2: growth stimuli (during the growth years)
3: pathological stimuli
what regulates cell division in most stabile cell populations (list)?
1: soluble stimulatory factors
2: soluble inhibitory factors
3: cell-cell contact (contact inhibition)
what can increase cell proliferation in order to repair damage (list)?
1: shortening cell cycle
2: pushing the stabile cells into the cell cycle
3: stimulating stem cells to generate parenchymal cells
describe the changes in the cell population in normal adult tissues?
there really isn’t any
remains static or self-sustaining
what are the receptor classes involved in transmembrane signaling (list)?
1: receptors with kinase activity
2: receptors without inherent catalytic function
3: g-protein coupled receptors
what are the transduction systems involved in transmembrane signaling?
1: MAP kinase (ras activation)
2: phosphoinositide-3 (PI-3) kinase (PIP2 and lipids)
3: inositol-lipid (IP3)
4: cyclic AMP (protein kinase A)
5: JAK/STAT
what types of pathways do kinase coupled receptors activate?
- PI3
- IP3
- MAPK
what type of factors activate kinase coupled receptors?
most growth factors
what pathways do receptors without kinase activity activate?
JAK/STAT pathways
what kinds of factors activate receptors without kinase activity?
cytokines
what is the down-stream effect of g-protein coupled receptors?
- release Ca2+ and/or generate cAMP
- changes cytoskeleton
what factors activate G-protein coupled receptors?
chemokines
what do kinases do?
put phosphates on proteins
what processes does wound healing involve?
- controlled cell division
- thrombosis
- cell migration
- differentiation
- secretion of new extracellular matrix components
what are the steps in wound healing?
- induction of an inflammatory process in response to the initial injury - thrombosis here
- removal of damaged or dead tissue
- proliferation and migration of parenchymal and connective tissue cells - fibroblasts predominately but macrophages too
- formation of new blood vessels and granulation tissue
- synthesis of ECM proteins and collagen deposition
- tissue remodeling
- wound contraction
- acquisition of wound strength
what are the key players in tissue repair and wound healing (list - summary card)?
1: leukocytes - predominately neutrophils and macrophages
2: coagulation cascade
3: extracellular matrix
4: cytokines
5: chemokines
6: growth factors
7: adhesion molecules
8: cell migration
what are integrins? (structure, location, function)
- heterodimers
- transmembrane proteins with laminin fibers on ends
- help cells connect to extracellular matrix
- can mediate cytoskeletal changes
what do integrins interact with?
ECM proteins including collagen, fibronectin, laminin, peptidoglycans
how do cells detect changes in their connectivity with the ECM?
integrins are connected to the cell’s cytoskeleton
if there’s a change in what the integrins are connected to outside of the cell, they can change their connections inside the cell
what are the components of the ECM? (list)
- collagen - elastin, fibrillin, and elastic fibers
- adhesive glycoproteins (fibronectin, laminin)
- matricellular proteins (SPARC (osteonectin, thrombospondins, osteopontin, tenacin)
- proteoglycans (heparan, condrotin, dermatan sulfates)
what does collagen I look like under EM?
dense periodicity long cables - each cable composed of three molecules wound together
how is collagen made?
- proteins synthesized in ER
- individual proteins capped at each end = prepropeptide
- cap keeps them from aggregating inside cell
- go to golgi - posttranslational modification - here they’re wound into helix (trimer)
- trimer with endcaps secreted into ECM as procollagen
- enzyme in ECM clips off cap - now they can aggregate
what builds up strength between collagen fibers?
crosslinking between lysines
what is the most abundant collagen? where is it found?
type I
ubiquitous - in skin, bone, etc.
what type of collagen is in scars?
collagen type I
where is collagen type II found?
- cartilage
- vitreous humor of eye
where is collagen type IV found?
basement membranes
how do basement membranes become specific for a particular organ (ie what makes them specific)?
depends on the procollagen that is combined to make the type IV collagen
what are the components of the basement membrane?
1: type IV collagen - various combinations of different chain types
2: laminin
3: entactin
4: heparan sulfate proteoglycan
what is laminin composed of (chains)? what is its structure? what is it necessary for?
one alpha chain, two beta chains
makes a cross structure
crticial for cell attachment
what is entactin?
- single polypeptide chain in surface of cell membrane
- interacts with glycoproteins on the outside
- function unknown
what are proteoglycans (structurally)? what do they do?
charged molecules with lots of sugars
laminin has binding sites for what molecules? which subunits contain which binding sites?
- collagen type IV on the B1 chain
- heparan sulfate on the A chain
- cell-binding domain at the point where all chains meet
where is fibronectin made? where is found in the body?
- made constitutively in the liver
- present in plasma
- leaks into tissue when there’s vascular leakage
what does fibronectin do?
- “glue”
- sticks everything together when there’s tissue damage
what can fibronectin bind to?
- heparan sulfate
- fibrin
- collagen
- integrin - where will bind to cells
how are proteoglycans arranged in the ECM?
- randomly
- loop between cells
what do proteoglycans in the ECM do?
- sugars bind GF, chemokines, some cytokines
- will allow for gradient of these signaling molecules to form
what are the mechanisms that are active in tissue damage (summary diagram)?
