Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP)

Barbas-Filho, João Valente; Ferreira, Marcelo Alves; Sesso, Antônio; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro; Capelozzi, Vera Luíza

doi:10.1136/jcp.54.2.132

Cited by 197 publications

(153 citation statements)

References 34 publications

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“…(25) Outros autores propuseram que a apoptose pode ser o evento primário na UIP. (27) Na fibrose pulmonar idiopática, embora a maior parte da fibrose seja composta de feixes de colágeno acelular, "velho", pequenos agregados de miofibroblastos e fibroblastos são muitas vezes identificados. Esses agregados, chamados focos fibroblásticos, são caracterizados por células fusiformes presentes em uma matriz mixóide frouxa, as quais são arranjadas paralelamente ao eixo longo dos septos alveolares.…”

Section: Discussionunclassified

Achados histológicos e sobrevida na fibrose pulmonar idiopática

Coletta¹,

Pereira

Ferreira

et al. 2003

J. Pneumologia

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Background: Idiopathic pulmonary fibrosis was recently redefined as usual interstitial pneumonia of unknown etiology. Consequently, the prognostic value of histological findings needs to be reassessed. Objective: To correlate clinical, functional and histological findings with survival in patients with idiopathic pulmonary fibrosis. Method: Patients (n = 51; mean age: 66 ± 8 years; gender: 21 females/30 males) were evaluated. Of the 51, 26 were smokers or ex-smokers. Duration of symptoms, forced vital capacity and smoking habits were recorded. All patients presented usual interstitial pneumonia verified through histology. Degree of honeycombing, established fibrosis, desquamation, cellularity, myointimal thickening of blood vessels and number of fibroblastic foci were graded according to the semiquantitative method. Results: Median duration of symptoms was 12 months and initial forced vital capacity was 72 ± 21%. Cox multivariate analysis revealed that survival correlated inversely and significantly (p < 0.05) with duration of symptoms and fibroblastic foci score, as well as with myointimal thickening of blood vessels. Limited numbers of fibroblastic foci, as well as myointimal thickening involving less than 50% of blood vessels, were predictive of greater survival. No correlation with survival was found for gender, age, forced vital capacity, inflammation or degree of cellularity. Conclusion: Semiquantitative analysis of lung biopsies yields relevant prognostic information regarding patients with usual interstitial pneumonia.

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Section: Discussionunclassified

Achados histológicos e sobrevida na fibrose pulmonar idiopática

Coletta¹,

Pereira

Ferreira

et al. 2003

J. Pneumologia

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“…Early ultrastructural studies described damage to the epithelium with reactive epithelial cells (15)(16)(17)(18). More recently, increased apoptosis of type II AECs has been demonstrated both in areas of IPF/UIP that appear histologically normal, without established fibrosis (19), and in epithelial cells overlying myofibroblasts (20). Increased expression of proapoptotic proteins and decreased expression of antiapoptotic proteins has also been reported (21).…”

Section: Apoptosis Of Aecs In Ipf What Is the In Vivo Evidence For Apmentioning

confidence: 95%

Evolving Concepts of Apoptosis in Idiopathic Pulmonary Fibrosis

Thannickal

Horowitz

2006

Proceedings of the American Thoracic Society

311

262

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Idiopathic pulmonary fibrosis (IPF) is a chronic, relentlessly progressive fibrosing disease of the lung of unknown etiology. Significant progress has been made in recent years in elucidating key aspects of the pathobiology of IPF. Insights into disease pathogenesis have come from studies of cell biology, growth factor/cytokine signaling, animal models of pulmonary fibrosis, and human IPF cells and tissue. A consistent finding in the ultrastructural pathology of IPF is alveolar epithelial cell injury and apoptosis. Another consistent finding in the histopathology of human IPF, described as usual interstitial pneumonia, is the accumulation of aggregates of myofibroblasts in fibroblastic foci. The extent or profusion of fibroblastic foci in lung biopsies is strongly correlated with increased mortality in patients with IPF. There is emerging evidence that myofibroblasts in IPF/usual interstitial pneumonia, both in the in vivo microenvironment and during the process of differentiation in vitro, acquire resistance to apoptosis. Here, we review the current evidence and mechanisms for this apparent "apoptosis paradox" in the pathogenesis of IPF.

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“…One of the main theories for the pathophysiology of idiopathic pulmonary fibrosis (IPF) is that injury to the pulmonary parenchyma causes epithelial cell damage and apoptosis [32]. Evidence of type II pneumocyte apoptosis in normal alveoli of IPF patients has been previously reported [33], and loss of alveolar epithelium, with failure of reepithelisation, was proposed to stimulate persistence and progression of fibrosis [32].…”

Section: Discussionmentioning

confidence: 99%

Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis

Fridlender¹,

Cohen²,

Golan³

et al. 2007

European Respiratory Journal

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Epithelial cell injury and apoptosis are recognised as early features in idiopathic pulmonary fibrosis and bleomycin-induced fibrosis in mice. Telomerase is a known apoptosisalleviating factor. The role of telomerase was studied during bleomycin-induced lung epithelial cell (LEC) apoptosis in vitro in a mouse LEC line, and in vivo in LECs isolated from bleomycintreated mice.The current authors evaluated changes in murine telomerase reverse transcriptase (mTERT) mRNA levels and changes in telomerase activity with the TRAPeze Detection Kit, telomeric length with the TeloTTAGGG Telomere Length Kit, and LEC apoptosis with FACScan and 4,6-diamino-2-phenylindole dihydrochloride stain.There was a significant elevation in mTERT mRNA and a transient 41% increase in telomerase activity 24 h after in vitro bleomycin treatment. At 72 h, telomerase activity had fallen to 26% below levels in untreated cells. Reduction of telomerase activity over time, or by direct inhibition, significantly elevated LEC apoptosis. No change in average telomeric length was noted. In vivo, telomerase activity of LECs from bleomycin-treated mice increased at 7 and 14 days.In conclusion, telomerase activity may play a protective role against robust bleomycin-induced lung epithelial cell apoptosis. Moreover, stabilising telomerase activity may decrease epithelial cell apoptosis and the resulting lung fibrosis.

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Evidence of type II pneumocyte apoptosis in the pathogenesis of idiopathic pulmonary fibrosis (IFP)/usual interstitial pneumonia (UIP)

Cited by 197 publications

References 34 publications

Achados histológicos e sobrevida na fibrose pulmonar idiopática

Achados histológicos e sobrevida na fibrose pulmonar idiopática

Evolving Concepts of Apoptosis in Idiopathic Pulmonary Fibrosis

Telomerase activity in bleomycin-induced epithelial cell apoptosis and lung fibrosis

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