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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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