- Title
- Regulation of cellular senescence is independent from profibrotic fibroblast-deposited ECM
- Creator
- Blokland, Kaj E. C.; Habibie, Habibie; Borghuis, Theo; Teitsma, Greta J.; Schuliga, Michael; Melgert, Barbro N.; Knight, Darryl A.; Brandsma, Corry-Anke; Pouwels, Simon D.; Burgess, Janette K.
- Relation
- Cells Vol. 10, Issue 7, no. 1628
- Publisher Link
- http://dx.doi.org/10.3390/cells10071628
- Publisher
- MDPI AG
- Resource Type
- journal article
- Date
- 2021
- Description
- Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor survival. Age is a major risk factor, and both alveolar epithelial cells and lung fibroblasts in this disease exhibit features of cellular senescence, a hallmark of ageing. Accumulation of fibrotic extracellular matrix (ECM) is a core feature of IPF and is likely to affect cell function. We hypothesize that aberrant ECM deposition augments fibroblast senescence, creating a perpetuating cycle favouring disease progression. In this study, primary lung fibroblasts were cultured on control and IPF-derived ECM from fibroblasts pretreated with or without profibrotic and prosenescent stimuli, and markers of senescence, fibrosis-associated gene expression and secretion of cytokines were measured. Untreated ECM derived from control or IPF fibroblasts had no effect on the main marker of senescence p16Ink4a and p21Waf1/Cip1. However, the expression of alpha smooth muscle actin (ACTA2) and proteoglycan decorin (DCN) increased in response to IPF-derived ECM. Production of the proinflammatory cytokines C-X-C Motif Chemokine Ligand 8 (CXCL8) by lung fibroblasts was upregulated in response to senescent and profibrotic-derived ECM. Finally, the profibrotic cytokines transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) were upregulated in response to both senescent- and profibrotic-derived ECM. In summary, ECM deposited by IPF fibroblasts does not induce cellular senescence, while there is upregulation of proinflammatory and profibrotic cytokines and differentiation into a myofibroblast phenotype in response to senescent- and profibrotic-derived ECM, which may contribute to progression of fibrosis in IPF.
- Subject
- extracellular matrix; senescence; idiopathic pulmonary fibrosis; proinflammatory; profibrotic; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1472562
- Identifier
- uon:48871
- Identifier
- ISSN:2073-4409
- Rights
- © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
- Language
- eng
- Full Text
- Reviewed
- Hits: 2929
- Visitors: 3029
- Downloads: 115
Collections
Goal 3: Good Health and Well-Being
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 2 MB | Adobe Acrobat PDF | View Details Download |