Ch3:Tissue Renewal, Regeneration, and Repair Flashcards Preview

Pathology > Ch3:Tissue Renewal, Regeneration, and Repair > Flashcards

Flashcards in Ch3:Tissue Renewal, Regeneration, and Repair Deck (102):
1

Two parts of tissue renewal?

1. Regeneration
2. Repair

2

What is regeneration?

Complete restitution of lost or damage tissue through proliferation of cells and tissues

3

What is the requirement for regeneration to occur?

Stem cells of tissues are not destroyed

4

What is repair?

Restoration of original structures but can be structurally deranged.

5

What does repair consist of?

Combination of regeneration and scar formation by the deposition of collagen

6

What is the predominant healing process that occurs when the extracellular matrix framework is damaged?

Scar formation

7

What is fibrosis?

Extensive deposition of collagen

8

Damage to the matrix (parenchymal stem cell matrix) results in what? 2

1. Fibrosis
2. Scar formation

9

The size of cell population is determined by what? (3)

Rates of:
1. Cell proliferation
2. Cell differentiation
3. Death by apoptosis

10

Cells incapable of replication are known as what?

Terminally differentiated cells

11

Proliferation of cells can be stimulated by what two types of conditions?

1. Physiologic
2. Pathogenic

12

What is epithelium?

A covering

13

What is mucosa?

Epithelium that absorbs and is moist

14

What are continuously dividing tissues called?

Labile

15

Examples of continuously dividing cells? 3

1. Epithelium/Mucosa
2. Hematopoietic cells
3. Mature cells derived from adult stem cells

16

What are quiescent tissues called?

Stable tissues

17

Level of replication in quiescent?
When can it speed up?

Low
In response to stimuli

18

Examples of quiescent cells? 3

1. Parenchymal cells of liver, kidney, pancreas
2. Mesenchymal cells
3. Vascular endothelium

19

Nondividing tissues are known as what?

Permanent tissues

20

Examples of permanent tissue? (3)

1. Neural tissue
2. Skeletal muscle
3. cardiac muscle

21

What is regenerative medicine?

Repairing damaged human tissues through stem cells

22

What makes stem cells so intriguing for repair? 2

1. Self-renewal properties
2. Capacity to generate differentiated cell lineages.

23

How is the replication of stem cells described?

Obligatory asymmetric replication

24

What is obligatory asymmetric replication?

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