Fibrillin‐1 staining anomalies are associated with increased staining for TGF‐β and elastic fibre degradation; new clues to the pathogenesis of emphysema

2009/03/02 by Mieke MJF Koenders, Mieke Koenders, Ronnie G. Wismans +8 · 8 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Biology #Cell biology #Chemistry #Congenital Diaphragmatic Hernia Studies #Connective tissue disorders research #Extracellular matrix #Fibrillin #Medicine #Neonatal Respiratory Health Research #Pathogenesis #Pathology #Staining #Transforming growth factor

paper · doi:10.1002/path.2548

openalex publication_date 2009/03/02 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/01

Abstract

We recently demonstrated aberrant staining of fibrillin-1 in lung tissue specimens with emphysematous lesions. In this study, we have extended this observation by an elaborate analysis of the elastic fibre. Using domain-specific antibodies to fibrillin-1, and to other elastin fibre-associated molecules, lung tissue derived from patients without obvious clinical emphysema, but harbouring various degrees of microscopical emphysematous lesions, was analysed. In addition, the fibrillin-regulated growth factor TGF-beta was studied. Electron microscopy and biochemical analysis of desmosine (a marker for elastin) were also performed. Results were compared with lung tissue derived from patients with clinical emphysema. Domain-specific antibodies recognizing the C-terminal, N-terminal, and middle part of fibrillin-1 showed aberrant staining patterns associated with increasing degrees of microscopical emphysema. Staining for elastin, emilin-1, and fibulin-2 was, however, not aberrant. TGF-beta staining was markedly increased. On the electron microscopic, but not light microscopical, level, initial elastic fibre degradation was noticed in specimens with microscopical emphysema. Lung specimens from patients with clinical emphysema also displayed fragmented fibrillin-1 staining and, in addition, displayed extensive degradation of the elastic fibre. The results suggest that fibrillin-1 anomalies and TGF-beta overexpression are associated with initial events occurring during the emphysematous process. Based on these and other data, a mechanism for emphysematogenesis is proposed.

Cited by

• Cigarette smoke exacerbates mouse allergic asthma through Smad proteins expressed in mast cells. [europepmc]
• Collagenase mRNA Overexpression and Decreased Extracellular Matrix Components Are Early Events in the Pathogenesis of Emphysema. [europepmc]
• Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome. [europepmc]
• Barriers to inhaled gene therapy of obstructive lung diseases: A review. [europepmc]
• Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases. [europepmc]
• Extracellular Matrix Component Remodeling in Respiratory Diseases: What Has Been Found in Clinical and Experimental Studies? [europepmc]
• Identification of hub genes and key pathways in the emphysema phenotype of COPD. [europepmc]
• Respiratory manifestations of Marfan syndrome: a narrative review. [europepmc]

Related

• Cellular Mechanisms of Tissue Fibrosis. 7. New insights into the cellular mechanisms of pulmonary fibrosis
• Pulmonary fibrosis: patterns and perpetrators
• Generation of a novel lung fibrosis model using precision-cut lung slices from transgenic TGFβ1 mice
• Lost after translation: insights from pulmonary surfactant for understanding the role of alveolar epithelial dysfunction and cellular quality control in fibrotic lung disease
• Epithelial–mesenchymal transition, a spectrum of states: Role in lung development, homeostasis, and disease