Title |
A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis
|
---|---|
Published in |
Respiratory Research, July 2018
|
DOI | 10.1186/s12931-018-0838-4 |
Pubmed ID | |
Authors |
John E. McDonough, Dries S. Martens, Naoya Tanabe, Farida Ahangari, Stijn E. Verleden, Karen Maes, Geert M. Verleden, Naftali Kaminski, James C. Hogg, Tim S. Nawrot, Wim A. Wuyts, Bart M. Vanaudenaerde |
Abstract |
Idiopathic pulmonary fibrosis is a fatal lung disease characterized by a progressive formation of fibroblastic foci in the interstitium. This disease is strongly associated with telomere dysfunction but the extent of telomere shortening and consequent chromosomal damage within IPF lungs and with regional disease severity remains unknown. Explanted IPF lungs (n = 10) were collected from transplant surgeries with six samples per lung analysed to capture the regional heterogeneity ranging from mild to severe disease. Non-used donor lungs (n = 6) were collected as "healthy" controls. Structural changes related to disease severity (microCT surface density), relative telomere length (real-time qPCR), and quantitative histology of chromosomal damage (γ-H2A.X) and extracellular matrix (elastin, total collagen, collagen 1, and collagen 3) were measured. A multivariate linear mixed-effects model controlling for subject was used to identify association of disease severity or fibrotic markers with telomere length and chromosomal damage. We observed shorter telomere length (p = 0.001) and increased chromosomal damage (p = 0.018) in IPF lungs compared to controls. In IPF lungs, telomere length was associated with total collagen (p < 0.001) but not with structural changes of disease severity. Chromosomal damage was positively associated with increased elastin (p = 0.006) and negatively with structural disease severity (p = 0.046). Extensive γ-H2A.X staining was also present in airway epithelial cells. Telomere length and chromosomal damage are involved in IPF with regional variation in telomere length and chromosomal damage associated with pathological changes in tissue structure and the extracellular matrix. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 24% |
Spain | 3 | 12% |
Ireland | 1 | 4% |
Mexico | 1 | 4% |
France | 1 | 4% |
Guinea | 1 | 4% |
Moldova, Republic of | 1 | 4% |
United Kingdom | 1 | 4% |
Canada | 1 | 4% |
Other | 0 | 0% |
Unknown | 9 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 17 | 68% |
Scientists | 5 | 20% |
Practitioners (doctors, other healthcare professionals) | 2 | 8% |
Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 53 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 8 | 15% |
Researcher | 7 | 13% |
Student > Master | 6 | 11% |
Other | 3 | 6% |
Student > Bachelor | 3 | 6% |
Other | 9 | 17% |
Unknown | 17 | 32% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 12 | 23% |
Biochemistry, Genetics and Molecular Biology | 10 | 19% |
Agricultural and Biological Sciences | 2 | 4% |
Nursing and Health Professions | 1 | 2% |
Unspecified | 1 | 2% |
Other | 5 | 9% |
Unknown | 22 | 42% |