Regeneração e Reparo Tecidual
Luiz Fernando Ferraz da Silva Curso de Patologia Geral – MPT0448 São Paulo, 1º de outubro de 2013
Balanรงo Proliferativo
Células e Arcabouços
Atividade proliferativa dos tecidos Lรกbeis Estรกveis Permanentes
Células Tronco ORIGEM Replicação assimétrica Diferenciação estocástica
Células Tronco Somáticas
O Ciclo Celular – Calma, sem traumas!!!
Fatores de Crescimento Growth Factor Epidermal growth α
Symbol EGF
Transforming growth factor α
TGF-α
Heparin-binding EGF HB-EGF Hepatocyte growth factor/scatter factor HGF
Vascular endothelial cell growth factor VEGF (isoforms A, B, C, D) Platelet-derived growth factor PDGF (isoforms A, B, C, D)
Fibroblast growth factor 1 (acidic), 2 (basic), and family
FGF
Transforming growth factor β (isoforms 1, 2, 3); other members of the family are BMPs and activin
TGF-β
Keratinocyte growth factor (also called KGF FGF-7) Tumor necrosis factor TNF
Source Platelets, macrophages, saliva, urine, milk, plasma
Functions Mitogenic for keratinocytes and fibroblasts; stimulates keratinocyte migration and granulation tissue formation Macrophages, T lymphocytes, keratinocytes, and Similar to EGF; stimulates replication of many tissues hepatocytes and most epithelial cells Macrophages, mesenchymal cells Keratinocyte replication Mesenchymal cells Enhances proliferation of hepatocytes, epithelial cells, and endothelial cells; increases cell motility, keratinocyte replication Many types of cells Increases vascular permeability; mitogenic for endothelial cells (see Table 3-3); angiogenesis Platelets, macrophages, endothelial cells, Chemotactic for PMNs, macrophages, fibroblasts, keratinocytes, smooth muscle cells and smooth muscle cells; activates PMNs, macrophages, and fibroblasts; mitogenic for fibroblasts, endothelial cells, and smooth muscle cells; stimulates production of MMPs, fibronectin, and HA; stimulates angiogenesis and wound contraction Macrophages, mast cells, T lymphocytes, Chemotactic for fibroblasts; mitogenic for endothelial cells, fibroblasts fibroblasts and keratinocytes; stimulates keratinocyte migration, angiogenesis, wound contraction, and matrix deposition Platelets, T lymphocytes, macrophages, Chemotactic for PMNs, macrophages, endothelial cells, keratinocytes, smooth muscle lymphocytes, fibroblasts, and smooth muscle cells, fibroblasts cells; stimulates TIMP synthesis, angiogenesis, and fibroplasia; inhibits production of MMPs and keratinocyte proliferation Fibroblasts Stimulates keratinocyte migration, proliferation, and differentiation Macrophages, mast cells, T lymphocytes Activates macrophages; regulates other cytokines; multiple functions
Sinalização
Transdução de sinais EGF, FGF, VEGF
Transdução de sinais EGF, FGF, VEGF
Adrenalina, Glucagon, Setoronina Citocinas
Regeneração x Reparo
TNF x TGF
Matriz Extracelular Suporte mecânico Controle de crescimento Manutenção da diferenciação Base para regeneração / reparo Microambientes teciduais Armazenamento de moléculas regulat
Matriz Extracelular
Matriz Extracelular
Reparo e cicatrização •Inflamação •Angiogênese •Migração e proliferação de fibroblastos •Formação da cicatriz •Remodelamento
AngiogĂŞnese
Cicatrização de Feridas
Cicatrização de Feridas
Cicatrização de Feridas
Reparo na Inflamação
Reparo na Inflamação
Reparo na Inflamação