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109 Cards in this Set

  • Front
  • Back
healing
repair involving combo of regeneration and CT deposition
scarring
this occurs when tissues are intrinsically unable to regenerate, if underlying CT scaffolding is disrupted or following extensive exudates
regeneration
cell or tissue growth that replaces lost structures; requires intact CT scaffolding
G0
quiescent cells are in this phase of the cell cycle
labile
type of tissue in which cells proliferate throughout life, replacing those that are destroyed
quiescent (stable)
type of tissue in which cells are normally involved in low-level replication but are capable of rapid division in response to stimuli
permanent
type of tissue in which cells cannot undergo division in postnatal life
stem cells
these cells are characterized by prolonged self-renewal and asymmetric replication
embryonic stem (ES) cells
these pleuripotent stem cells are capable of differentiating into any tissue type
adult stem cells
these are cells located in reservoirs in normal adult tissue and have a restricted differentiation capability; lineage-specific
hematopoietic stem cells (mesodermal lineage cells)
these cells are capable of transdifferentiation into neurons, hepatocytes and other adult cell lineages
plasticity
breadth of differentiation potential
multipotent adult progenitor cells (MAPCs)
these cells proliferate in culture without senescence and have broad developmental capacity; they are found in bone marrow and multiple other tissue sites
tissue stem cells
these are typically responsible for generating the mature cells of the organ in which they reside
canals of Hering (junction of hepatocytes and bile duct system); oval cells
liver stem cells reside here and give rise to these
satellite stem cells
regeneraton of injured skeletal muscle is accomplished by profieration of ___
proliferation, cell movement, contractility, differentiation and angiogenesis
growth factors affect these processes of wound healing:
epidermal and transforming growth factors (EGF ad TGF)
these GFs exert their activity by binding to transmembrane molecules with intrinsic tyrosine kinase activity
hepatocyte GF (HGF)
this growth factor is produced by fibroblasts, endo cells and hepatocytes; also promotes embryonic development
vascular endo GF (VEGF)
growth factors that promote BV formation in early development and new BV growth
vasculogenesis
BV formation in early development
angiogenesis
new BV growth in adults
platelet-derived GF (PDGF)
this GF is found in platelet alpha granules and made by other cells; cause migration of fibroblasts, monocytes and smooth muscle cells
fibroblast GF (FGF)
these GFs bind to extracellular matrix heparan sulfate to form reservoirs of inactive fafctors
TGF-beta
GF that inhibits most epithelial cells and is an anti-inflam; promotes fibrosis
bind target cell receptors, transmit intracellular signal (dimerization) to induce gene transcription and promote entry into cell cycle
How do GFs signal for their activity?
intrinsic tyrosine kinase which phosphorylate effector molecules
receptors with intrinsic kinase activity associate with and activate:
cytosolic protein kinases (JAKs that link activated receptors with STATs)
receptor without intrinsic kinase activity associate with and activate
a signal transducing G protein complex generating intracellular second messengers
ligand binding of G protein-linked receptors activates:
Ca and cAMP
What are the second messengers associated with G protein-linked receptors?
PI3 kinase, MAP-kinase and IP3
What are the 3 pathways a ligand can follow when binding to a receptor with intrinsic tyrosine kinase activity?
MAP-kinase pathway
Which intrinsic tyrosine kinase pathway is associated with Ras/Raf?
steroid hormones are lipophilic so they diffuse through the membrane
How are steroid hormone receptors different than GF receptors?
DNA binding and transcriptional regulation
transcription factors have separate domains for
post-translational modifications
When transcription factors act do they rely on new synthesis or post-translational modifications?
phosphorylation, release of constitutively bound inhibitors, dimerization
What are some types of post-translational modifications?
p53; DNA damage
this tumor suppressor gene is activated in response to _____ and inhibits further progression through cell cycle
collagen
these CT proteins provide tensile strength
triple helix and 3 polypeptide chains with glycine-X-Y repeating sequence
basic structure of collagen
1,2,3,5,11
these are the fibrillar collagens
1
collagen of skin and bone is mostly
2
collagen of cartilage is mostly
4
this collagen type forms fibrils and is found in BMs
extracellular space
the terminal fragments of collagen are cleaved in this area:
vit C
this vitamin is required to cross-link and stabilize fibrils
elastin
inherited defects in fibrillin result in formation of abnormal ____
immunoglobulin, cadherins, integrins and selectrins
4 main families of cell adhesion proteins
cadherins
these mediate Ca-dep interactions with the same kind of receptor on cells; play a major role in cell motility and differentiation
integrins
these participate in cell-cell adhesion and adhesion to ECM
fibronectin and laminin
What do integrins bind to in the ECM?
ligand binding to integrins causing clustering
focal adhesion complexes are formed by:
osteonectin
this adhesion molecule is also known as SPARC and contributes to tissue remodeling after injury; is an angiogenesis inhibitor
osteopontin
this adhesion molecule regulates calcification and also mediates leukocyte migration
proteoglycan and hyaluronic acid
these ECM components have a core protein linked to 1 or more GAGs
hyaluronic acid
this ECM component binds large amounts of water
fibrosis
ECM deposition during chronic inflammation
inflammatory response; proliferation and migration of CT cells; angiogenesis and formation of granulation tissue; synthesis of ECM proteins; tissue remodeling, wound contraction
healing sequence:
granulation tissue
hallmark of healing; involves proliferation of fibroblasts and vascular EC
new vessels that are leaky
edema occurs in healing due to:
branching of preexisting vessels and recruitment of endo precursor cells from bone marrow
angiogenesis occurs due to:
hemangioblast
this precursor generates both hematopoietic stem cells and angioblasts in embryonic development
plasminogen activator
this disrupts EC cell-cell contact during angiogenesis
VEGF and angiopoietins
these are the most important growth
factors in angiogenesis
fibroblast migration and proliferation; ECM deposition; tissue remodeling
3 steps in scar formation:
fibroblasts and collagen
scar replaces granulation tissue and is composed mainly of what?
matrix metalloproteinases (MMPs)
these enzymes degrade ECM
matrix metalloproteinases (MMPs)
these enzymes require zinc for action
tissue inhibitors of metalloproteinases (TIMP)
these inhibit the enzymes that degrade ECM
those with opposed edges (surgical)
these types of wounds heal by first intention:
wound contraction through the activity of myofibroblasts
this is characteristic of second intention would healing:
10%
when sutures are removed, wound strength is:
70-80%
the plateau of wound strength is:
inadequate granulation tissue or collagen deposition
this causes wound dehiscence or ulceration
Lamellipodia are cell membrane extensions that power the locomotion of leukocytes
What are lamellipodia and what do they do?
Via integrins
How do the leading edges of in migrating cells adhere to the extracellular matrix?
They anchor actin stress fibers
How do the cytoplasmic domains of integrins function
Perlecan
Which extracellular matrix constituents modulates the network of associations among the other extracellular matrix constituents?
Alpha helix
What is the tertiary structure of collagen fibrils?
Mature collagens are trimers of three alpha chains that form a triple helix
How do collagen fibrils differ from mature collagens?
Non-fibrillar collagens have globular domains that interrupt the triple helical segments
How do fibrillar collagens differ from non-fibrillar collagens?
It’s hyrophobicity, extensive covalent cross linking, and resistance to most proteolytic enzymes
What factors are important in the stability of elastin?
Laminins are hetero trimers that are the principal basement membrane glycoproteins
What are the structure and function of laminins?
As alternate splicing products of the same gene
How are the different fibronectins synthesized?
The glycosaminoglycan chains
Which moieties(functional groups) are most responsible for the different functional characteristics of proteoglycans?
Protein tyrosine kinase receptors for peptide growth factors, g protein coupled receptors for chemokines and intgrin receptors for extracellular matrix
Which three receptor systems are key to initiating cell proliferation, migration, and gene expression in wound healing?
Scar formation
What is the predominant form of repair following an inflammatory response?
The temporary extracellular organization of plasma derived matrix proteins and tissue derived components that accumulate at sites of injury
What is provisional matrix?
The transient specialized repair mechanism that replaces provisional matrix
What is granulation tissue?
Type three collagen
What is the first type of collagen produced by fibroblasts during repair?
Vascular endothelial growth factor or VEG-F
What is the most important soluble mediator of angiogenesis?
This association determines blood vessel patterning in wound healing
What is the main effect of the association of VEG-F and glycosaminoglycans?
Adherin’s junctions
Which structures are made up of cadherin receptors?
Re-epithelialization occurs by immigration of epidermal cells that begin at the wound margins
How are wounds re-epithelialized and where does the process begin?
By assembly of actin fibers when integrin fibers bind to fibronectin and other matrix molecules
How is the epithelial cell mobility activated?
A population of stem cells with a potential to differentiate and replicate
What type of cell is necessary if regeneration is to occur?
From preimplantation blastocysts
From where do embryonic stem cells derive?
Although pluripotent stem cells may differentiate into many different types of tissues, totipotent stem cells may differentiate into all tissues
How are totipotent stem cells different from pluripotent stem cells?
A scar restores anatomic integrity to the injured area while fibrosis interferes with the functionality of the injured structure
How does scarring differ from fibrosis?
Oval cells
Hepatic injury as in fulminate (severe and sudden onset) hepatitis may lead to liver regeneration because of which cell population?
Corticorenal tubles
Restoration of renal tissue is most likely to occur when which portion of the nephron is injured?
Alveolar type II cells
What cell type is capable of re-epithelializing alveoli denuded of their lining cells?
Wounds in the first two trimesters tend to heal without scarring
Referring to interuterine injury, how do wounds to a fetus during the first two trimesters of pregnancy differ from those that occur afterwards?
Increased mechanical stress on a wound
What is the most common factor leading to wound dehiscence?
Because of inadequate intrinsic blood supply, or poor revascularization during healing
Why does ulceration of a wound generally occur?
collagen formation
neutralization of TGF will affect which inflam-response step?
collagen deposition
corticosteroids affect what part of the healing process?
integrin
intracytoplasmic cytoskeletal elements (like actin) interact with the ECM through this molecule to provide attachment and migration
ras proteins
What protein is involved in transducing the mitogenic signal from epidermal cell membrane to the nuclus?
basic fibroblast GF (bFGF)
What factor is most important in angiogenesis?