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119 Cards in this Set

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  • Back
What are the two organs that undergo any sort of regeneration? What type of regeneration is it?
1. Liver and kidney
2. Compensatory hypertrophy
Healing is usually a tissue response to what three things?
1. Wound
2. Inflammation in an internal organ
3. Cell necrosis in organs that cannot regerate
Healing can be broken down into what two phases?
1. Regeneration
2. Scar formation
Inflammation of the lining of internal organs usually heals in what way?
Scarring
What is the replacesment of inflammatory infiltrates with granulation tissue called?
Organization
Scarring occurs when the tissue that is damaged lacks an intact _______ .
ECM scaffold
In adult tissues, what three factors determine the population size?
1. Proliferation rate
2. Differentiation
3. Apoptosis
What type of cell can replace some terminally differentiated cells?
Stem cells
What is an example of physiologic cell proliferation becomes pathologic?
Benign Prostatic Hyperplasia
What is the number one factor involved with proliferation of tissues?
Activation of quiescent cells
What are the three categories of tissues in terms of their division rates?
1. Quiescent tissues - low levels of replication
2. Continuosly dividing tissues - surface epithelia and bone marrow; most cells derived from stem cells
3. Non-dividing tissues - cells in these tissues have left the cell cycle; skeletal, cardiac or neurons
What are two properties of stem cells that make them unique?
1. Prolonged self-renewal
2. Asymmetric replication
How would you describe an embryonic stem cell (ESC) and where can you isolate them?
1. Pluripotent
2. Blastocyst
What can you attribute a ESCs pluripotentcy to?
That activation of certain trascription factors like Nanog and Wnt-Beta-Catnin.
What type of cells have limited division capacity and are lineage specific?
Adult stem cells
What are stem cells outside the bone marrow called?
Tissue stem cells
What is the name of the location where one can fine stem cells?
Niches
What type of cells regenerate/generate all types of blood cells and reconstitute bone marrow after irridation?
Hematopoietic Stem Cells
What are three ways to collect HSC?
1. Tapping Marrow
2. From the umbilical cord
3. From circulation after treatment with the cytokine GMCSF
What type of cells do bone marrow stromal cells give rise to(5)?
1. Chondrocytes
2. Osteoblasts
3. Adipocytes
4. Myoblasts
5. Endotheilial cell precursors
A change in a stem cell differentiation from one cell type to another is called?
Transdifferentiation
A cell that can differentiate into multiple cell lines is said to have _______ .
Developmental Plasticity
What are the heterogeneous group of stem cells that have broad differentiation capabilities that are adult bone marrow called?
Multipotent Adult Progentitor Cells
Where do liver stem cells reside? What type of cells do they differentiate into? What do those cells turn into?
1. Canals of Hering
2. Oval cells
3. Hepatocytes and biliary cells
When is the only time when liver stem cells are used?
When normal liver cell proliferation is blocked.
Where are neural stem cells located in the brain and what was used as the marker to locate them?
1. Dentate gyrus and olfactory bulb
2. Nestin
In the renewal of epithelial tissue, cell numbers are increased by what methods?
1. Increasing the number of dividing stem cells
2. Increasing the number of replications in the amplification compartment
3. Shortening the replication time
Growth factors have effects on what five areas?
1. Proliferation
2. Locomotion
3. Contractibility
4. Differentiation
5. Angiogenesis
What two growth factors share the same receptor? What are their basic functions? How does their receptor work? What is their main receptor?
1. TGF-Alpha - proliferation of epithelial tissue
2. EGF - Mitogenic for a variety of different cells
3. Tyrosine Kinase activity
4. EGFR1
What growth factor acts as a morphogen in embyronic development that causes cell scattering and migration? 2. What is another name for the GF? Its receptor is a product of what protoonco gene?
1. Hepatocyte Growth Factor (HGF)
2. Scatter factor
3. c-MET
What two processes is VEGF protent in stimulating? What action do its receptors signal through? What is the main receptor? Which VEGF binds to it?
1. Angiogenesis and Vasculogenesis
2. Tyrosine kinase receptors
3. VEGFR-2
4. VEGF-A
Which VEGF receptor can be used in the mobilization of stem cells and inflammation? What type of VEGF binds to this receptor?
1. VEGFR-1
2. VEGF-B
Which receptors and VEGF are used for the production of lymphatics?
1. VEGFR-3 with VEGF-C and VEGF-D
What does platelet derived growth factor do? What is the main cell that releases PDGF? PDGF can be responsible for what condition and why?
1. Causes the migration and proliferation of fibroblasts, smooth muscle and monocytes
2. Platelets upon activation
3. Liver fibrosis by activating stellate cell proliferation
PDGF is made up of how many chains? How many surface receptors does PDGF have?
1. Two; A and B (AA BB AB)
2. Two alpha and beta
What are four functions of Fibroblast Growth Factor?
1. Angiogenesis: FGF-2
2. Wound repair
3. Development - skelatal muscle and lung development for example
4. Hematopoesis
Which FGF is a monocyet differentiation blocker?
FGF-6
How many isoforms are there of TGF-Beta? Which isoform is the most widespread? Is TGF-B active when secreted?
1. Three TGF-B(1-3)
2. TGF-B1
3. No
Describe what happens when TGF-B binds to its receptor?
1. TGF-B binds to a type II receptor which binds to a type I receptor (serine/threonine)
2. This leads to the P of smad2 and smad 3.
3. They form dimers with smad 4 and become TFs
Does TGF have many funtions?
Yes it is considered pleiotropic with a vengence
Does TGF-B promote or inhibit epithelial and leukocyte growth? If you lose TGF-B recptors you can develop what?
1. Inhibit - inhibits Cip/Kip and INK/ARF
2. Cancer
What effect does TGF-B have on fibroblasts and smooth muscle?
Increases their proliferation - it is a potent fibrogenic agent
Is TGF-B pro or anti inflammatory?
Anti-inflammatory
In basic terms, growth factors do two things. What are they?
1. Up-regulate transcription
2. Allow the cell to move into the next step in the cell cycle
What type of cell signalling is typically used in tissue repair of wounds? It is also used in hepatocyte replication.
Paracrine
What type of cell signalling is occuring when a molecule is anchored in the cell membrane for signalling purposes?
Juxtacrine signalling
True or false: most signal transduction pathways involve the dimer or trimerization of receptors?
True
What type of receptor do all of the growth factors use along with insulin?
Tyrosine-Kinase
Basically what happens when a Tyrosine-Kinase receptor is activated?
Dimerization which allows cross P which acivates the kinase activity.
What are three other molecules/enzymes used in tyrosine-kinase signalling?
1. Phospholipase C
2. PI3K - activates Kinase-Akt
3. GRB-2 and SOS
The activation of Kinase Akt results in what two things? What else is it used in?
1. Increased cell proliferation and decreased apoptosis
2. Insulin signalling
GRB-2 and SOS end up activating what? Then that molecule makes what?
1. MAP-Kinase
2. TFs FOS and JUN
Cytokines, interferons, erythropoientin, GSCF, GH and prolactin signal through what system? In this system, what is produced?
1. JAK/STATs
2. STATS act as TFs
Where do breast cancer steroid receptors bind?
In the cytoplasm of the cell instead of the nucleus.
When a rapid response is needed, are new TFs made? What happens?
1. No existing ones are used
2. They are modified
What type of genes are directly related to the proliferation of cells?
Proto-onco genes
What two things generally stimulate a cell to replicate?
1. Growth factors
2. Signalling of ECM components through integrins
What point in the cell cycle is known as the rate limiting restriction point? What regulates this step
1. G1/S point
2. CDK that bind cyclins and end up P proteins needed for the transcription
What is the role of Rb in replication?
When activated, it P EF2 so that it no longer works. When P by the CDK/cyclin complex, Rb no longer can P EF2
If there are mistakes in the replication of cell DNA, what initates apoptosis?
p53
Most tissue regeneration is what? What does it end up restoring?
1. Compensatory hypertrophy or hyperplasia
2. Function not anatomy
What is attributed to the lack of true regeneration in human tissues?
Rapid scarring
What five organs are the only ones with regenerative capabilities?
1. Kideny
2. Liver
3. Adrenal gland
4. Thyroid
5. Pancreas
In liver regeneration, hepatocytes move from what stage in the cell cyle to what stage in the cell cycle?
1. G0 to G1
What is special about the wave of proliferation of the hepatocytes and non-parenchymal cells?
It is synchronized.
What is hepatocyte replication dependent on?
Paracrine effects of growth factors and cytokines released by non-parenchymal cells
What are the two major cell cyle restriction points in liver regeneration and what cytokines/GF are associted with each?
1. G0/G1: IL-1 and TNF
2. G1/S: HGF TGF-Alpha
What CDK-Cyclin complexes helps move the cell at the G1/S point?
1. CyclinD-CDK4: P of Rb
2. CyclinE-CDK2
What is the primer for replication in liver regeneration? What does it cause the release of for the G1/S phase?
1. TNF
2. HGF release and TGF-Alpha activation
What are the three macromolecules that constitute ECM?
1. Fibrous structural proteins
2. Adhesive glycoproteins
3. Proteoglycans and hyaluronic acid
What is the amino acid sequence that makes collagen unique?
Gly-X-Y
What type of collagen is amorphous and where is it seen?
1. Type IV
2. Basement membrane
What other compound is seen in the basement membrane with Type IV collagen?
Laminin
What enzyme crosslinks collagen? What substance is required for cross-linking? What disorder is a result of a lack of this substance?
1. Lysyl Oxidase
2. Vitamin C
3. Scurvy
What are three disorders that involve collagen? Which collagens do they involve?
1. Scurvy - Vit C def.
2. Ehlers Danlos - Type I, III and IV collagens
3. Osteogenesis imperfecta - Type I collagen
What type of fibers allow for tissue recoil?
Elastic fibers
What syndrome is marked by a mutation in elastic fibers?
Marfan Syndrome
What are the four familes of CAM that can act as a receptor or protein?
1. Integrin
2. Selectin
3. Immunoglobin
4. Cadherins
What are two examples of ECM proteins that integrins bind to?
1. Fibronectin
2. Laminin
What is tissue fibronectin used in? What is plasma fibronectin used in?
1. Wound healing
2. Clotting
What is the most abundant ECM protein in the basement membrane? What does it bind to?
1. Laminin
2. Type IV collagen
What allows the transmission of enviromental signals to the cell for the releasal of growth factors?
Integrins binding with actin and intermediate filaments
What is the name for the area where clusters of receptors for certain ligand localize? What are some cytoskeletal proteins that localize here?
1. Focal adhesion complexes
2. Talin, vinculin and paxillin
What class of molecules link cadherins with actin?
Catenins
What molecule can be a regulator of nuclear transcription and is involved with cancer?
Free B-Catenin
What does SPARC/Osteonectin and Thrombospondins do?
Angiogenesis inhibitor
What does osteopontin do?
Regulates calcification
What does tanacin do?
Regulates morphogensis and cell adhesion
What is a proteoglycan? What are the most common? What do they do?
1. Protein + GAG
2. Heparan sulfate, chondriotin sulfate and dermatin sulfate
3. Regulate tissue structure/permeability and modulate cell growth and differentiation
What is the main function of hyaluronic acid. What is another function? What surface glycoprotein on leukocytes binds HA?
1. Binds lots of H2O and becomes a viscous gel for joint (cartilage)
2. Prevents migrating cells from binding to other cells
3. CD44
What two processes are going on at once during fibrosis?
1. Wound healing and wound damage
What is a hallmark for healing? When is its production begun? What are its key features?
1. Granulation tissue
2. 24h after insult
3. Angiogenesis and proliferation of fibroblasts
Can angiogenesis occur from the recruitment of endothelial progenitor cells?
Yes
What is the common precursor cell in HSC and Angioblasts?
Hemangioblast
What do angioblasts form?
1. New vessels, pericytes and smooth muscle from the vessel
It is now known that what angioblast-like cells are stored in bone marrow and called upon when needed?
Endothelial Progentitor Cells
Which VEGFR is the most important in angiogenesis and what does it bind?
1. VEGFR-2
2. VEGF-A
What happens in the basic model of angiogenesis? What is a second option?
1. VEGF stimulates the migration of EPCs from bone marrow to the site. These cells form a capillary plexus that matures into mature vessels.
2. VEGF can cause the mobilization of endothelial cells from existing vessels to form new ones
What must new vessels be supported by?
1. Pericytes
2. Smooth muscle
3. ECM
What are four stabilizing factors of new vessels and their function?
1. Ang1 - interacts with Tie2 to recruit pericytes
2. Ang2 - interacts with Tie2 to loosen vessels to be more reactive with VEGF
3. PDGF - recruits smooth muscle cells
4. TGF-B - recruits ECM proteins
What can cause venous malformations?
Abscence of Tie2
In fibroblast migration and proliferation, what causes the increased vascular permeability that allows proteins like fibrinogen and fibronectin to enter the area?
VEGF
What cytokines are active in the migration and proliferation of fibroblasts in scar formation?
1. IL-1
2. TNF
What is the most important growth factor in inflammatory fibrosis? Why?
1. TGF-B
2. Because it big in the recruitment of cells needed for fibrosis and it also is a chemotactic for monocytes and causes angiogenesis
What is the main component of the formation of the actual scar? When does the laying of collagen begin?
1. Fibrillar Collagen
2. 3-5 days after insult
The balance between ECM synthesis and degradation is referred to as ________.
Remodeling
ECM degradation is achieved by what enzymes? They are dependent on what metal?
1. MMP
2. Zinc
How are MMPs synthesized?
1. Propeptides which means they need to be activated
What inhibits MMP secretion? What also inhibits the actions of collagenases?
1. TGF-B
2. Tissue Inhibitors of MMPs
What are the actions of ADAM enzymes? What defiency leads to embryonic death by pulmonary hypolasia?
1. They cleave the membrane bound forms of GFs allowing to be become free.
2. ADAM-17
Why do fetal cutaneous wounds heal with no scarring and little inflammation?
They have a different isoform of TGF-B.
What is hallmark of healing by second intention?
Wound contracture
What is the maximal strength of a wound after healing?
About 70% of normal strength
Steroids can activate what recepor that is important in the cellular differentiation of adipocytes?
Peroxisome Proliferator Activated Receptors
White is a primer for cellular replication in liver damage? What does it do?
1. TNF
2. Upregulates everything needed for replication
3. Causes the release of HGF and the activation of TNF-Alpha
What is a key ECM protein that mediates angiogenesis?
1. Alpha v Beta 3
2. Interacts with MMP-2, regulates VEGFR-2, mediates adhesion to ECM components such as fibronectin, thrombospondin and osteopontin
Fibroblast Migration and Proliferation is triggered by what six factors?
1. TGF-B
2. IL-1
3. TNF
4. PDGF
5. FGF
6. EGF
Ulceration is usually due to what?
Inadequate vascularization
What deficiency causes great contracture in mice?
MMP3 (Stromelysin-1)