特发性肺纤维化的病理机制
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Pathogenesis Mechanism of IPF
Outline
Part 1
Introduction Pathophysiologic Mechanisms Perspective
Part 2
Part 3
Introduction(1)
Interstitial lung diseases(ILDs):diffuse parenchymal lung diseases
Initiation stage(1):
TGF-β activation
TGF-β
AECs
• TGF-β1 • TGF-β2 • TGF-β3
Normal condition
TGFห้องสมุดไป่ตู้β+LAP
Epithelial cell
• direct IPF? • profibrotic process • EMT
Genetic predisposition、UPR, TGF-βand EMT
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79
Introduction(4)
R. M. du Bois.Strategies for treating idiopathicpulmonary fibrosis.2010.9:129-40
Pathophysiologic Mechanisms
Physiologic stages
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79
Progression stage(1): mensenchymal cells and matrix remodeling
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79
Hidenori Kage and Zea Borok.EMT and Interstitial Lung Disease: A Mysterious Relationship.Curr Opin Pulm Med. Sep 2012; 18(5): 517–523.
Initiation stage(4):
Progression stage(2):
Epigenetics
Yang IV, Schwartz DA. 2011. Epigenetic control of gene expression in the lung. Am. J. Respir. Crit. Care Med. 183:1295 –301
LAP:latency-associated peptide RGD:arginine-glycineaspartate
• Integrin αvβ6 increase • RGD • TGF-β1、TGF-β3 activation
Initiation stage(2):
Endoplasmic reticulum stress(ER stress)
fibrosis of alveolar interstitium and adjacent structures
impair gas exchange Etiology:enviromental exposures,systemic disease,isolated and sporadic
disease without extrapulmonary involvement
Mark P. Steele and David A. Schwartz.Molecular Mechanisms in Progressive Idiopathic Pulmonary Fibosis.Annu.Rev.Med.2013.64:265-76
Introduction(2)
Idiopathic pulmonary fibrosis(IPF):poor prognosis 71% of total cases 50% motality rate three years after diagnosis Pathology:usual interstitial pneumonia
Mark P. Steele and David A. Schwartz.Molecular Mechanisms in Progressive Idiopathic Pulmonary Fibosis.Annu.Rev.Med.2013.64:265-76
Introduction(3)
R. M. du Bois.Strategies for treating idiopathicpulmonary fibrosis.2010.9:129-40
UPR
(Unfoldde protein response)
Click to add Title
P Walter, and D Ron Science 2011;334:1081-1086
Initiation stage(3):
Epithelial-to-mesenchymal transition(EMT)
Predisposition stage:
Genetics
Familial pulmonary fibrosis (FPF) Chromosome 11: marker D11S1318, with a LOD score of 3.3
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79
Outline
Part 1
Introduction Pathophysiologic Mechanisms Perspective
Part 2
Part 3
Introduction(1)
Interstitial lung diseases(ILDs):diffuse parenchymal lung diseases
Initiation stage(1):
TGF-β activation
TGF-β
AECs
• TGF-β1 • TGF-β2 • TGF-β3
Normal condition
TGFห้องสมุดไป่ตู้β+LAP
Epithelial cell
• direct IPF? • profibrotic process • EMT
Genetic predisposition、UPR, TGF-βand EMT
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79
Introduction(4)
R. M. du Bois.Strategies for treating idiopathicpulmonary fibrosis.2010.9:129-40
Pathophysiologic Mechanisms
Physiologic stages
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79
Progression stage(1): mensenchymal cells and matrix remodeling
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79
Hidenori Kage and Zea Borok.EMT and Interstitial Lung Disease: A Mysterious Relationship.Curr Opin Pulm Med. Sep 2012; 18(5): 517–523.
Initiation stage(4):
Progression stage(2):
Epigenetics
Yang IV, Schwartz DA. 2011. Epigenetic control of gene expression in the lung. Am. J. Respir. Crit. Care Med. 183:1295 –301
LAP:latency-associated peptide RGD:arginine-glycineaspartate
• Integrin αvβ6 increase • RGD • TGF-β1、TGF-β3 activation
Initiation stage(2):
Endoplasmic reticulum stress(ER stress)
fibrosis of alveolar interstitium and adjacent structures
impair gas exchange Etiology:enviromental exposures,systemic disease,isolated and sporadic
disease without extrapulmonary involvement
Mark P. Steele and David A. Schwartz.Molecular Mechanisms in Progressive Idiopathic Pulmonary Fibosis.Annu.Rev.Med.2013.64:265-76
Introduction(2)
Idiopathic pulmonary fibrosis(IPF):poor prognosis 71% of total cases 50% motality rate three years after diagnosis Pathology:usual interstitial pneumonia
Mark P. Steele and David A. Schwartz.Molecular Mechanisms in Progressive Idiopathic Pulmonary Fibosis.Annu.Rev.Med.2013.64:265-76
Introduction(3)
R. M. du Bois.Strategies for treating idiopathicpulmonary fibrosis.2010.9:129-40
UPR
(Unfoldde protein response)
Click to add Title
P Walter, and D Ron Science 2011;334:1081-1086
Initiation stage(3):
Epithelial-to-mesenchymal transition(EMT)
Predisposition stage:
Genetics
Familial pulmonary fibrosis (FPF) Chromosome 11: marker D11S1318, with a LOD score of 3.3
Paul J. Wolters and Harold R. Collard. Pathogenesis of Idiopathic Pulmonary Fibrosis. Annu. Rev. Pathol. Mech. Dis. 2014. 9:157–79