Age-associated differences in the human lung extracellular matrix
(2023) In American Journal of Physiology - Lung Cellular and Molecular Physiology 324(5). p.799-814- Abstract
Extracellular matrix (ECM) remodeling has been associated with chronic lung diseases. However, information about specific age-associated differences in lung ECM is currently limited. In this study, we aimed to identify and localize age-associated ECM differences in human lungs using comprehensive transcriptomic, proteomic, and immunohistochemical analyses. Our previously identified age-associated gene expression signature of the lung was re-analyzed limiting it to an aging signature based on 270 control patients (37–80 years) and focused on the Matrisome core geneset using geneset enrichment analysis. To validate the age-associated transcriptomic differences on protein level, we compared the age-associated ECM genes (false discovery... (More)
Extracellular matrix (ECM) remodeling has been associated with chronic lung diseases. However, information about specific age-associated differences in lung ECM is currently limited. In this study, we aimed to identify and localize age-associated ECM differences in human lungs using comprehensive transcriptomic, proteomic, and immunohistochemical analyses. Our previously identified age-associated gene expression signature of the lung was re-analyzed limiting it to an aging signature based on 270 control patients (37–80 years) and focused on the Matrisome core geneset using geneset enrichment analysis. To validate the age-associated transcriptomic differences on protein level, we compared the age-associated ECM genes (false discovery rate, FDR < 0.05) with a profile of age-associated proteins identified from a lung tissue proteomics dataset from nine control patients (49–76 years) (FDR < 0.05). Extensive immunohistochemical analysis was used to localize and semi-quantify the age-associated ECM differences in lung tissues from 62 control patients (18–82 years). Comparative analysis of transcriptomic and proteomic data identified seven ECM proteins with higher expression with age at both gene and protein levels: COL1A1, COL6A1, COL6A2, COL14A1, FBLN2, LTBP4, and LUM. With immunohistochemistry, we demonstrated higher protein levels with age for COL6A2 in whole tissue, parenchyma, airway wall, and blood vessel, for COL14A1 and LUM in bronchial epithelium, and COL1A1 in lung parenchyma. Our study revealed that higher age is associated with lung ECM remodeling, with specific differences occurring in defined regions within the lung. These differences may affect lung structure and physiology with aging and as such may increase susceptibility to developing chronic lung diseases.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- aging, airway wall, extracellular matrix, lung, parenchyma
- in
- American Journal of Physiology - Lung Cellular and Molecular Physiology
- volume
- 324
- issue
- 5
- pages
- 799 - 814
- publisher
- American Physiological Society
- external identifiers
-
- pmid:37039368
- scopus:85159741642
- ISSN
- 1040-0605
- DOI
- 10.1152/ajplung.00334.2022
- language
- English
- LU publication?
- yes
- id
- 15a38bee-152e-447d-9b3e-85b430146938
- date added to LUP
- 2023-08-22 09:01:28
- date last changed
- 2024-04-20 01:11:37
@article{15a38bee-152e-447d-9b3e-85b430146938,
abstract = {{<p>Extracellular matrix (ECM) remodeling has been associated with chronic lung diseases. However, information about specific age-associated differences in lung ECM is currently limited. In this study, we aimed to identify and localize age-associated ECM differences in human lungs using comprehensive transcriptomic, proteomic, and immunohistochemical analyses. Our previously identified age-associated gene expression signature of the lung was re-analyzed limiting it to an aging signature based on 270 control patients (37–80 years) and focused on the Matrisome core geneset using geneset enrichment analysis. To validate the age-associated transcriptomic differences on protein level, we compared the age-associated ECM genes (false discovery rate, FDR < 0.05) with a profile of age-associated proteins identified from a lung tissue proteomics dataset from nine control patients (49–76 years) (FDR < 0.05). Extensive immunohistochemical analysis was used to localize and semi-quantify the age-associated ECM differences in lung tissues from 62 control patients (18–82 years). Comparative analysis of transcriptomic and proteomic data identified seven ECM proteins with higher expression with age at both gene and protein levels: COL1A1, COL6A1, COL6A2, COL14A1, FBLN2, LTBP4, and LUM. With immunohistochemistry, we demonstrated higher protein levels with age for COL6A2 in whole tissue, parenchyma, airway wall, and blood vessel, for COL14A1 and LUM in bronchial epithelium, and COL1A1 in lung parenchyma. Our study revealed that higher age is associated with lung ECM remodeling, with specific differences occurring in defined regions within the lung. These differences may affect lung structure and physiology with aging and as such may increase susceptibility to developing chronic lung diseases.</p>}},
author = {{Ngassie, Maunick Lefin Koloko and De Vries, Maaike and Borghuis, Theo and Timens, Wim and Sin, Don D. and Nickle, David and Joubert, Philippe and Horvatovich, Peter and Marko-Varga, György and Teske, Jacob J. and Vonk, Judith M. and Gosens, Reinoud and Prakash, Y. S. and Burgess, Janette K. and Brandsma, Corry Anke}},
issn = {{1040-0605}},
keywords = {{aging; airway wall; extracellular matrix; lung; parenchyma}},
language = {{eng}},
number = {{5}},
pages = {{799--814}},
publisher = {{American Physiological Society}},
series = {{American Journal of Physiology - Lung Cellular and Molecular Physiology}},
title = {{Age-associated differences in the human lung extracellular matrix}},
url = {{http://dx.doi.org/10.1152/ajplung.00334.2022}},
doi = {{10.1152/ajplung.00334.2022}},
volume = {{324}},
year = {{2023}},
}