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92 Cards in this Set

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What is the difference between regeneration and repair?
regeneration refers to plaement of lost structures (hepatocytes). repair is some regeneration, but also scar tissue
What is fibrosis?
deposition of collagen that occurs during persistent injury or infection.
What are terminally differentiated cells?
cells that cannot differentiate into anything further
What are labile tissues?
continuously dividing tissues
What are quiescent (stable) tissues?
tissues that are normally very slowly proliferating, but can be increased by stimulus
What are "permanent" tissues?
non-dividing tissues; out of the cell cycle (e.g. neurons
What cells allow for skeletal muscle regeneration?
satellite cells
What type of cells are skeletal muscle? (continuous, quiscent or non-dividing)?
non-dividing
What type of cells are hepatocytes? (continuous, quiscent or non-dividing)?
quiescent. normally don't proliferate much, but if the liver is partially removed, they increase proliferation
In obligatory asymmetric replication by stem cells, what are the 2 cell products after division?
one stem cell retains its ability to serve as a stem cell. the other enters a differentiation pathway
In stochastic differentiation by stem cells, what are the 2 cell products after division?
either both cells differentiate or both cells remain stem cells
Which has a greater potential for differentiation (can become more things)? pluripotent or multipotent cells?
pluripotent is less differentiated and can become anything. a multipotent cell is more restricted
What is transdifferentiation?
change in lineage commitment of a stem cell
What are induced pluripotent stem (iPS) cells?
differentiated stem cells become stem cells by inducing embryonic stem cell genes/signals/transcription factors
What cells regulate stem cell renewal and progeny cell formation for somatic cells?
niche cells for particular areas of the body
Embryonic cells are from what part of the early embryo?
inner cell mass of blastocyst (pluripotent)
What is the function of the "Nanog" gene in embryonic stem cells?
prevent differentiation
4 major transcription factors induced in iPS cells and found naturally in embryonic stem cells?
Oct 3/4, SOX-2, c-myc, Klf4
What are transit amplifying cells?
from adult somatic stem cells and give rise to progenitors
What does "developmental plasticity" refer to?
the ability for cells to transdifferentiate. cells can change their lineages during development, hence the word "plasticity"
2 types of stem cells found in bone marrow?
Hematopoietic stem cells and marrow stromal cells
What are "oval cells"?
hepatocyte progenitors
Do neurons regenerate in adult brains?
apparently they do. neural precursor cells have been found in multiple locations of the brain
3 areas where stem cells are found in epidermis
hair follicle, interfollicular surface epidermis, sebaceous glands
Skin epidermis and intestinal epithelium proliferation/differentiation is regulated by what 2 pathways?
Wnt pathway and inhibition of BMP (bone morphogenic protein) pathway
Skeletal muscle does not divide, but do regenerate. How do we get new skeletal muscle?
satellite cells proliferate ("notch" signaling) and become new skeletal muscle cells
Where are "limbal stem cells" found?
between cornea and conjunctiva
Where is the major checkpoint/restriction point in the cell cycle?
G1/S transition
What proteins regulate the cell cycle?
cyclins, CDKs (cyclin dependent kinases)
How do CDKs progress a cell through the cell cycle?
phosphorylating proteins that regulate the cycle (e.g. RB protein)
Describe the role of RB (restinoblastoma) protein in regulation of the cell cycle.
RB protein is usually bound to the E2F transcription factor and prevents the cell cycle. CDK phosphorylates it and releases it, activating E2F = transcription = cell cycle
With regard to the cell cycle, what is senescence?
damaged cells enter G0 or apoptosis to prevent further damage
Epidermal Growth Factor (EGF) uses what type of receptor?
intrinsic tyrosine kinase receptors
Function of hepatocyte growth factor?
stimulate hepatocyte mitosis
PDGF function
stimulate clotting and bring inflammatory cells (macrophges etc.) to the site of clotting for wound healing and inflammation
VEGF function
vasculogenesis (new blood vessels) and angiogenesis (branching blood vessels). also increases endothelial permeability during inflammation
VEGF uses what type of receptors
tyrosine kinase
Fibroblast growth factor is released to promote what types of general activity?
wound repair, angiogenesis, hematopoiesis, development
TGF-B uses what receptors?
serine threonine kinase receptors (Smad pathway)
TGF-B inhibits growth of what cells?
most epithelial cells. less TGF-B = more tumor risk
TGF-B main function
promote fibrogenic changes/tissue repair. more fibroblasts, less collagen degrading, less proteases
What is autocrine cell signaling?
cells signal themselves to produce a product/react
What is paracrine cell signaling?
cells release a signal into interstitial fluid and nearby cells respond
What is endocrine cell signaling?
cells release hormones into bloodstream that all cells can respond to (if they have the receptors for it)
TGF-A uses what type of receptor?
tyrosine kinase. (TGF-B uses serine-threonine kinase)
Describe the prototype pathway for a receptor with intrinsic tyrosine kinase activity.
hormone binds, receptor dimerizes, receptor, auto-phosphorylates, GRB2 binds SOS binds RAS binds RAF/MAPK. kinase cascade occurs
Function of PLC (phospholipase C)
convert PIP2 into IP3 and DAG
Function of IP3
binds sarcoplasmic reticulum and release calcium into cytosol. this calcium now signals more pathways
Function of diacylglycerol (DAG)
activate Protein kinase C
Function of PI3 Kinase
convert PIP2 into PIP3 to help Protein kinase B/Akt pathway
Growth hormone, immune cytokines and prolactin uses what type of receptor?
JAK/STAT (recruit tyrosine kinase)
Describe the JAK/STAT pathway
Hormone binds, JAK recruited, phosphorylation to bind and activate STATs. STAT dimerizes and enters nucleus to regulate transcription
Which type of receptors signal a cAMP dependent cascade?
heptahelical G-protein receptors
Where are steroid hormone receptors found on/in a cell?
in cytosol or in the nucleus
How do activated steroid hormone receptors regulate transcription?
by binding to Hormone Responsive Elements on the DNA
What is compensatory hyperplasia in the liver?
After liver lobe removal, the lobes still remaining proliferate to regenerate liver cells
During compensatory growth of the liver after partial resection, what cells give rise to the new hepatocytes?
the normal remaining hepatocytes (once quiescent) will now replicate a few times to create more new hepatocytes, then return to quiescence. Contrary to popular belief, stem cells/progenitors are not involved in this process
3 major groups found in ECM
Collagen fibers, adhesive proteins, proteoglycans
Most common protein in the animal world.
Collagen
Collagen type found in the basement membrane
4, form sheets instead of fibers
Type 2 collagen is mostly found in ...
cartilage
Why does low vitamin C lead to scurvy or poor wound healing?
vitamin C is needed for hydroxylation of procollagen during collagen I synthesis. without hydroxyl groups, the collagen is less stable due to less hydrogen bonding
Marfan's syndrome is characterized by a defect in what protein?
fibrillin, a major component of elastin
Why do patients with Marfan's syndrome have aortic dissection?
aorta has lost is elasticity and cannot expand during high systolic pressure so it ruptures
Cadherins, integrins and selectins are part of what family of the ECM?
cell adhesion molecules
2 major components of basement membranes?
collagen 4 and laminin
How does the ECM work to regulate cell function?
the integrins and receptors can send signals to the nucleus
Contact inhibition is regulated by what proteins in the ECM?
catenins and cadherins
Function of proteoglycans
made up of GAGs which hold water. proteoglycans lubricate and resist/cushion forces
Why would metalloprotesases be needed during angiogenesis?
to degrade the endothelial basement membrane to branch a new vessel
In a patient withe recent ischemia, what do we expect to see with regard to their EPC (endothelial precursor cells)?
high levels, suggesting angiogenesis is occurring
Blockage of DLL4 (Delta like ligand) during angiogenesis has what effect on proliferation?
increases
Blockage of DLL4 (Delta like ligand) during angiogenesis has what effect on sprouting?
increases
Blockage of DLL4 (Delta like ligand) during angiogenesis has what effect on vascular organization?
decreases
Major function of DLL4 during angiogenesis
orientation /organization of newly formed vessels
Blockage of VEGF during angiogenesis has what effect on proliferation?
decreases
VEGF is regulated by HIF-1. What is HIF-1?
hypoxia induced factor released during hypoxia
Once a new blood vessel is formed, what do tie2, Ang1/2 need to do?
stabilize the weak vessel
3 phases of cutaneous wound healing
inflammation, proliferation, maturation
Purpose of a blood clot during wound healing.
stop bleeding and serve as scaffold for tissue repair/ inflammatory cells
Which type of wound would be more likely to have granulation tissue? primary or secondary union?
secondary union = more tissue damage than primary. more tissue damage = more granulation tissue to repair the tissue
Most important fibrogenic agent
TGF-B
What is wound contraction?
occurs to close larger wounds on the surface; myofibroblasts and actin do this
What comes first? Granulation tissue or scar?
granulation tissue
The replacement of granulation tissue with a scar is called...
connective tissue remodeling; ECM will be made and destroyed
How can nutrition affect wound healing?
poor vitamin C = bad collagen
How can infection impede wound healing?
persistent inflammation
What is wound dehiscence?
opening of a healing wound due to poor granulation tissue/scar formation
What is a keloid?
a hypertropic scar due to high tissue healing;
What is wound contracture?
exaggerated healing process resulting in deformaties
Tissue repair is stimulated by macrophages activated (classically or alternatively)?
alternatively (by IL-4, IL-13)
Function of osteopontin (OPN)
promote wound healing; mediates myofibroblast differentiation by TGF-B