# Regulation of cellular senescence is independent from profibrotic fibroblast-deposited ECM
> Blokland K.E.C.

URL kanonis: https://discover.unhas.ac.id/publications/regulation-of-cellular-senescence-is-independent-from-profibrotic-fibroblast-dep
Jurnal / Konferensi: Cells
Tahun terbit: 2021
DOI: https://doi.org/10.3390/cells10071628
ISSN: 20734409
Kuartil SJR: Q1
Citations: 16

## Authors
- Blokland K.E.C.

## Abstract
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 p16<sup>Ink4a</sup> and p21<sup>Waf1/Cip1</sup>. 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.

## Keywords
- Decorin
- Proinflammatory cytokine
- CTGF
- Extracellular matrix
- Idiopathic pulmonary fibrosis
- Senescence
- Cell biology
- Fibroblast
- Fibrosis
- Myofibroblast
- Cancer research
- Downregulation and upregulation
- Pulmonary fibrosis
- Biology
- Growth factor
- Immunology
- Pathology
- Internal medicine
- Medicine
- Proteoglycan
- Inflammation
- Lung
- Cell culture
- Receptor
- Genetics
- Biochemistry
- Gene

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Sumber: Discover Unhas — RIMS Universitas Hasanuddin.
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