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3 Healing and Repair 57
4. Increased levels of cyclin A bound to CDK2 initiates DNA duplication in the nucleus.
5. The levels of mitotic or B cyclins rise in the M phase and the M-phase promoting factor
(the complex of mitotic B cyclins with the M-phase CDK or CDK1) initiates the forma-
tion of the mitotic spindle, condensation of the chromatin as well as dissolution of the
nuclear envelope.
Q. Enumerate the growth factors and cytokines involved in
regeneration and wound healing.
Ans. Growth factors (GFs) are mostly proteins that prolong survival and induce proliferation
of specific cells (Table 3.1). They bind to specific receptors and deliver signals that stimulate
expression of genes whose products induce growth. They have the following functions:
1. Cell cycle activation (by direct stimulation or removal of blocks that inhibit cell cycle)
2. Prevention of apoptosis
3. Enhanced synthesis of cellular proteins
TABLE 3.1. Growth factors and cytokines involved in regeneration and wound healing
Type of growth
factor Symbol Receptor Sources Functions
Epidermal growth EGF EGFR1 (ERBB1) Platelets, macrophages, Mitogenic for keratinocytes
factor salivary glands, and fibroblasts; stimulates
keratinocytes, etc. keratinocyte migration and
granulation tissue formation
Fibroblast growth FGF FGFRs (1-4) Platelets and macro- Wound repair. angiogenesis
factor (FGF) family phages
Transforming growth TGF-a ERB B2 (HER-2 Activated macrophages, Similar to EGF; stimulates
factor-a or HER-2/Neu) T lymphocytes, kera- replication of hepatocytes
tinocytes, etc. and many epithelial cells
Hepatocyte growth HGF/SF c-MET Mesenchymal cells Enhances proliferation of epi-
factor/scatter factor thelial and endothelial cells
Vascular endothelial VEGF VEGFR-1, Mesenchymal cells Increases vascular permea-
cell growth factor VEGFR-2 and bility; mitogenic for endo-
(isoforms A, B, C VEGFR-3 thelial cells
and D)
Platelet-derived PDGF PDGFR a and b Platelets, macrophages, Chemotactic for neutrophils,
growth factor endothelial cells, ke- macrophages and smooth
(isoforms A, B, C ratinocytes, smooth muscle cells; stimulates
and D) muscle cells production of matrix me-
talloproteinases (MMPs),
fibronectin, stimulates
angiogenesis
Tumour necrosis TNF TNF-R Macrophages, mast Activates macrophages;
factor cells, T lymphocytes regulates other cytokines
Interleukins ILs IL-R Macrophages, mast Chemotactic, angiogenic;
cells, lymphocytes regulate other cytokines
and many tissues
Transforming growth TGF-b TGF-b receptors Platelets, T lympho- Chemotactic, angiogenic,
factor-b (TGF-b (types I and II) cytes, macrophages, mitogenic for fibroblasts,
isoforms - TGF-b1, endothelial cells stimulates wound contrac-
TGF-b2 and TGF- tion, and matrix deposition
b3)
Interferons IFN-a Interferon Lymphocytes and Activate macrophages, inhibit
receptors fibroblasts fibroblast proliferation,
regulate other cytokines
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