Term
| What is the functional difference between integrins and cadherins? |
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Definition
- Integrins bind ECM components such as actin
- Cadherins bind other cells for cell/cell adhesion (desmosomes and adherens junctions) |
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Term
| Which cell types are self-renewing? |
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Definition
1) Epidermal keratinocytes
2) Intestinal epithelium
3) Blood forming tissues |
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Term
| Which cell types are "potentially renewable cells." That is, quiescent until a some stimuli. |
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Definition
1) Dermal fibroblasts
2) Endothelial cells of blood vessels
** Remember, these cells can be de-differentiated in response to certain signals ** |
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Term
| Which cell types are "non-renewing" or permanent. |
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Definition
1) Adipocites
2) Neurons (can still regrow axons and dendrites, if cell body is unharmed)
3) Muscle cells of heart
4) Auditory hair cells of the ear. |
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Term
| What are the 3 M's of the cellular response to injury? |
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Definition
1) Migration
2) MItosis
3) Maturation |
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Term
| How do injured basal keratinocytes migrate? |
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Definition
AIM- get the cells free, stop them from dividing, grow things that let them move and move them along ECM components to target.
1) Decrease desmosomes and cell surface integrins (laminin) to let cells free
2) Reorganize actin microfilaments to form lamellipodia and inhibit mitosis.
3) Increase gap junctions and protease secretion for cell-cell communication and path-making.
4) Increase Integrins for collagen type 1 and fibronectin |
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Term
| How do injured basal keratinocytes divide? |
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Definition
1) Increase GF and GFR expression
2) Remove mitotic inhibition from migration stage
3) New epithelium stratify and build new desmosomes
4) Synthesis of nasement membrane proteins, Bullous pemphigoid antigen (BPA) and collagen type IV. |
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Term
| How do injured basal keratinocytes that have divided proceed to maturation? |
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Definition
1) Stratification and differentiation of new epidermis
2) Restored barrier (specialized function)
3) Re-formed basement membrane with hemidesmosomes
4) Synthesis of BM laminin and increased integrin for laminin (anchors new cells)
5) Restoration of rete ridges, normal architecture with transient hypertrophy. |
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Term
| Explain the course of the acute inflammatory response. |
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Definition
Short- Clot formation (1st)....Neutrophils and macrophages digest.........Granulation tissue formation (2nd)......Fibroblast-mediated collagen deposition under clot (3rd)
1) Platelet release and aggregation causes fibrin clot formation, which stops blood flow (1st provisional matrix of wound healing)
2) Neutrophils enter endothelial cells via diapedis and phagocytose bacteria.
3) Monocytes are recruited and become macrophages, which finish up the neutrophil's job, and add signaling factors.
4) Granulation tissue (2nd matrix of dermal repair) forms as a loose connective tissue composed of blood vessels, macrophages and fibroblasts (not much collagen).
5) Fibroblasts deposit new collagen on under the clot (3rd matrix of dermal repair), using granulation tissue as a scaffold. |
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Term
| What are the 3 matrices of dermal wound healing? |
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Definition
1) Fibrin clot
2) Granulation tissu
3) Fibroblast-dependent collagen deposition on clot. |
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Term
| Explain the 3 M's of Connective Tissue Wound Healing |
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Definition
1) Migration- chemotaxis of fibroblasts to would site with selective integrin-expression for path-finding.
2) Mitosis- Increased GF release acts on granulation tissue and leads to increased proliferation and fibroblast density (i.e. metabolism) in wound site.
4) Maturation- ECM, protease and GF synthesis
Increased actin microfilaments along membranes leading to specialized cell-cell attachments for coordinated wound healing.
Decrease in cell density by apoptosis with extended remodeling of scar tissue |
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Term
| Why is scar tissue referred to as "repaired" tissue rather than "regenerate" tissue. |
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Definition
| Granulation tissue is gradually filled by collagenous matrix (mediated by recruited fibroblasts) that is functionally adequate, but not structurally and functionally equivalent to native tissue. |
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Term
| What migration events occur during dermal angiogenesis? |
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Definition
SHORT
-Wound exudate leaks out and is amplified
- Plasminogen is activated to plasmin which activates collagenase
- collagenase and endothelial-secreted proteases digest BM
- Endothelia cells migrate into tissue towards firbronectin, FGF and VEGF
1) Plasma that leaks out of wound forms "exudate" which is amplified by fibronectin fragments, fibroblast growth factors and heparin.
2) Plasminogen activator and plasminogen leak into tissue, where plasminogen is converted to plasmin (active protease)
3) Plasmin activates laten collagenase, which attacks the BM around capillaries and small vessels( Endothelial cels release proteases to help).
4) Endothelial cells migrate through weak spots in BM in response to fibronectin fragments, FGF and VEGF. |
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Term
| What mitosis and maturation events occur during dermal angiogenesis? |
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Definition
1) Mitosis
-FGF, IGF and VEGF cause endothelial proliferation (entered wound during migration). Endothelial cells also release GFs for autoinduction.
-Capillary buds appear in granulation tissue (hypertrophy)
2) Maturation- Buds join to form capillary loops that establish circulation and oxygen-mediated remodeling occurs to prune vessels through apoptosis (Wound Granulation Tissue becomes less metabolically active). |
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Term
| What is the primary difference between epithelial and endothelial wound healing? |
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Definition
Epithelia involves re-epithelialization
Endothelial involves neo-vascularization |
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Term
| What are 2 limits of known wound repair mechanisms? |
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Definition
1) Scar tissue is imperfect (abnormal elastin proteoglycans, sub-c fat and muscle)
2) Fibrosis can occur (parenchyma are replaced by collagenous connective tissue, or "stroma"). Eventually, organ failure can occur. |
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Term
| How does the regulation of TGF-B and IL-10 relate to wound healing and repair? |
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Definition
1) TGF-B is master frowth factor (modulates others). Its sustained production causes fibrosis (neutralizing Ab reduce scarring), but it is necessary for maturation.
2) IL-10 is important for terminating the inflammatory response |
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Term
| How is Fetal Wound healing "regenerative," while adult wound healing is "reparative"? |
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Definition
No Fibrosis and Reduced Inflammation
1) Absence of Fibrosis- TGFB, Receptors and Modulators
-Scarless wound healing from greater TGF-B3:TGF-B1 ratio.
- TGFB1R and TGFB2R can only be down-regulated in fetal wound response, and not in adult.
- Fibromodulin and Decorin (modulators of TGF-B signaling) change from fetal to adult
2) Reduced Inflammation- IL-10 is critical for shutting off inflammation |
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Term
| Which Growth Factors, Activity Modulators and ECM components are important for wound healing? |
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Definition
GFs- TGF-B (scarring) and IL-10 (inflammation)
AMs- Plasmin (activates collagenase), MMPs (path-finding), TIMPs, Thymosins, microRNAs (transcriptional regulation)
ECM- Fibronectin (path-finding), Collagen (3rd matrix), Fibromodulin and Decorin (TGF-B) |
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