Ch3:Tissue Renewal, Regeneration, and Repair Flashcards
(102 cards)
1
Q
Two parts of tissue renewal?
A
- Regeneration
2. Repair
2
Q
What is regeneration?
A
Complete restitution of lost or damage tissue through proliferation of cells and tissues
3
Q
What is the requirement for regeneration to occur?
A
Stem cells of tissues are not destroyed
4
Q
What is repair?
A
Restoration of original structures but can be structurally deranged.
5
Q
What does repair consist of?
A
Combination of regeneration and scar formation by the deposition of collagen
6
Q
What is the predominant healing process that occurs when the extracellular matrix framework is damaged?
A
Scar formation
7
Q
What is fibrosis?
A
Extensive deposition of collagen
8
Q
Damage to the matrix (parenchymal stem cell matrix) results in what? 2
A
- Fibrosis
2. Scar formation
9
Q
The size of cell population is determined by what? (3)
A
Rates of:
- Cell proliferation
- Cell differentiation
- Death by apoptosis
10
Q
Cells incapable of replication are known as what?
A
Terminally differentiated cells
11
Q
Proliferation of cells can be stimulated by what two types of conditions?
A
- Physiologic
2. Pathogenic
12
Q
What is epithelium?
A
A covering
13
Q
What is mucosa?
A
Epithelium that absorbs and is moist
14
Q
What are continuously dividing tissues called?
A
Labile
15
Q
Examples of continuously dividing cells? 3
A
- Epithelium/Mucosa
- Hematopoietic cells
- Mature cells derived from adult stem cells
16
Q
What are quiescent tissues called?
A
Stable tissues
17
Q
Level of replication in quiescent?
When can it speed up?
A
Low
In response to stimuli
18
Q
Examples of quiescent cells? 3
A
- Parenchymal cells of liver, kidney, pancreas
- Mesenchymal cells
- Vascular endothelium
19
Q
Nondividing tissues are known as what?
A
Permanent tissues
20
Q
Examples of permanent tissue? (3)
A
- Neural tissue
- Skeletal muscle
- cardiac muscle
21
Q
What is regenerative medicine?
A
Repairing damaged human tissues through stem cells
22
Q
What makes stem cells so intriguing for repair? 2
A
- Self-renewal properties
2. Capacity to generate differentiated cell lineages.
23
Q
How is the replication of stem cells described?
A
Obligatory asymmetric replication
24
Q
What is obligatory asymmetric replication?
A
Each stem cell division, one of the daughter cells retains its self-renewing capacity while the other enters differentiation pathway
25
How is the ratio of stem cells/differentiated cells described?
Stochastic differentiation
26
What is stochastic differentiation?
Population if maintained by the balance between stem cells divisions that generate either two self-renewing stem cells or two cell that will differentiate
27
Stem cells that can generate all tissues of the body are known as what?
Pluripotent
28
Examples of pluripotent cells? 2
Embryonic cells
| Induced pluripotent stem cells (iPS)
29
Where do adult stem cells reside?
Niches
30
What makes up a niche?
Mesenchymal, endothelial, and other cell types
31
Niche cells do what?
Generate or transmit stimuli that regulate stem cell self-renewal and generationi of progeny cells
32
Embryonic stem cells are found where?
Inner cell mass of blastocysts in early embryonic development
33
Research applications of embryonic stem cells? 3
1. Study specific signals and differentiation steps required for a tissue
2. Production of knockout or knockin mice
3. Repopulate damaged organs
34
Result of reprogramming differentiated cells?
Induced pluripotent stem cells
35
What is reproductive cloning?
Transfer of nuclear material into oocyte
36
How effective is therapeutic and reproductive cloning?
| Why?
Inefficient
Deficiency in histone methylation results in improper gene expression
37
What does the pluripotency of cells in a clone depend on?
Expression of four transcription factors known as oncogenes
38
What are transit amplifyin cells?
Rapidly dividing cells generated from somatic stem cells
39
What is transdifferentiation?
Change in the differentiation of a cell from one type to another
40
What is special about hemopoietic stem cells?
Can differentiate into hepatocytes and neurons upon fusion with already differentiated cells of target tissue
41
What is developmental plasticity?
Ability of cell to transdifferentiate into diverse lineages
42
How might HSC's be involved in repair/immune?
Migrate to site of inflammation and generate innate immune cells, release GF's and cyotkines for promoting repair
43
Stem cells in bone marrow include? (2)
1. HSC's
| 2. MSC's
44
What do HSC's generate in bone marrow?
All blood cell lineages
45
What do MSC's generate in bone marrow?
Chondrocytes, osteoblasts, adipocytes, myoblasts, and endothelial cell precursors
46
Stem cells in liver are found where?
| Differentiate into what
Canals of Hering (oval cells)
| Hepatocytes and biliary cells
47
Stem cells in the brain are called what?
Neural stem cells
48
Where are stem cells in the skin? 3
Hair follicle bulge, interfollicular layers of epidermis, and sebaceous glands
49
Replication of cells in cell cycle is stimulated by what? 92)
1. Growth factors
| 2. Signaling from ECM components through integrins
50
Components of cell cycle? 4
1. G1 (presynthetic)
2. S (DNA synthesis)
3. G2 (premitotic)
4. M (mitotic phases)
51
When do most controls of cell cycle act?
Between G1 and S phase at restriction point
52
Progression in cell cycle regulated by what?
1. Cyclins
| 2. Cyclin-dependent kinases
53
What do CDK's do?
Bind and form complexes with cyclins
| Phosphorylate cell cycle inhibition proteins such as RB
54
How does RB inhibit cell cycle?
Forms tight inactive complex with TF E2F
55
What will inhibit CDKs? And when?
CDK inhibitors at checkpoints
56
What regulates the CDK inhibitors?
Growth factors
57
Senescence or apoptosis is triggered via what?
p53-dependent mechanisms
58
Proliferation of cells is driven mainly by what?
Growth factors
59
What effects can growth factors have? 4
1. Promote survival
2. Affect locomotion, contractility
3. Affect cellular differentiation
4. Promote angiogenesis
60
How do growth factors act?
Ligands that stimulate transcription of genes
61
Epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) share what?
Common receptor (EGFR) family of four membrane receptors with intrinsic tyrosine kinase activity
62
EGFR1 mutations/amplification result in what?
Cancers of lung, head, neck, breast, glioblastomas, and others
63
ERB B2 receptor is overexpressed in what?
Breast cancer
64
Hepatocyte growth factor (HGF) has what receptor?
c-MET
65
c-MET is highly expressed or mutated in what
Tumors of renal and thyroid papillae
66
HGF is identical to what?
Scatter factor for fibroblast
67
Is HGF important?
Required for survival during embryonic development
68
Platelet derived growth factor binds to what?
PDGFR alpha and Beta
69
Where is PDGF stored?
| When is it released?
Platelet granules
Upon platelet activation
70
Effect of PDGF?
Migration and proliferation of fibroblasts, smooth muscle cells, and monocytes to areas of inflammation and healing of skin wounds
71
How many forms of VEGF are there?
5
72
Effect of VEGF? 2
Vasculogenesis and angiogenesis in chronic inflammation, healing of wounds, and in tumors
73
Fibroblast growth factor includes how many members?
20
74
What is FGF-7 known as?
Keratinocyte growth factor?
75
What FGF works in wound repair? (2)
FGF-2 and KGF re-epithelialize skin wounds
76
What FGF works in angiogenesis?
FGF-2
77
What are four main functions of FGF?
Wound repair
angiogenesis
Hematopoiesis
Development of muscle and lung
78
What is a growth inhibitor for most epithelial cells?
TGF-Beta
79
TGF-Beta is what type of agent?
Pathologically involved in what?
Potent fibrogenic agent
Fibrosis in chronic inflammatory conditions and hypertrophic scars
80
Is TGF-beta involved in immune response?
Strong anti-inflammatory BUT might enhance some immune functions
81
What is autocrine signaling?
Cells respond to molecule that they themselves secrete
82
Examples of autocrine signaling? 2
Liver generation
| Tumors
83
What is paracrine signaling?
One cell type produces the ligand which in turn acts on adjacent cells
84
Example of paracrine signaling?
CT repair and wound healing
85
What is endocrine signaling?
Hormones synthesized by cells of endocrine organs act on target cells distant from site of synthesis
86
Main receptor types? (4)
1. Tyrosine kinase activity receptors
2. Receptors that recruit kinases
3. G-protein-coupled receptors
4. Steroid hormone receptors
87
Example of receptors with intrinsic tyrosine kinase?
1. Growth factors
88
Ligand binding in tyrosine kinase receptors causes what? (3)
1. Dimerization of receptor
2. Tyrosine phosphorylation
3. Activation of receptor tyrosine kinase
89
Example of receptors that recruit kinases?
Cytokine
90
Cytokine receptors transmit signals to nucleus by what?
JAK/STAT pathway
91
G-coupled protein receptors are used by what?
Endocrine ligands
92
How do g-coupled protein receptors transmit signals?
Trimeric GTP-binding proteins
93
What is the largest family of plasma membrane receptors?
G-protein coupled receptors
94
Defects in G-coupled receptors result in what?
Retinitis pigmentosa, corticotropin deficiencies, and hyperparathyroidism
95
Steroid hormone receptors are found where?
Nucleus
96
Ligands that bind to steroid hormone receptors include what? (3)
1. Thyroid hormone
2. Vitamin D
3. Retinoids
97
What is one special branch of steroid hormone receptors?
| And they are involved in what?
Peroxisome proliferator-activated receptors
Adipogenesis, inflammation, and atherosclerosis
98
Transcription factors do what mainly?
Modulate gene activity
99
Growth promoting genes include? (2)
c-MYC
| c-JUN
100
Cell cycle-inhibiting gene?
p53
101
Why can't mammals regenerate limbs or organs?
Absence of blastema formation
102
What is similar to regeneration that mammals can do?
Compensatory hyperplasia
