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Matrisome Properties of Scaffolds Direct Fibroblasts in Idiopathic Pulmonary Fibrosis

Elowsson Rendin, Linda LU ; Löfdahl, Anna LU ; Åhrman, Emma LU ; Müller, Catharina LU ; Notermans, Thomas LU ; Michaliková, Barbora ; Rosmark, Oskar LU ; Zhou, Xiao-Hong ; Dellgren, Göran and Silverborn, Martin , et al. (2019) In International Journal of Molecular Sciences 20(16).
Abstract

In idiopathic pulmonary fibrosis (IPF) structural properties of the extracellular matrix (ECM) are altered and influence cellular responses through cell-matrix interactions. Scaffolds (decellularized tissue) derived from subpleural healthy and IPF lungs were examined regarding biomechanical properties and ECM composition of proteins (the matrisome). Scaffolds were repopulated with healthy fibroblasts cultured under static stretch with heavy isotope amino acids (SILAC), to examine newly synthesized proteins over time. IPF scaffolds were characterized by increased tissue density, stiffness, ultimate force, and differential expressions of matrisome proteins compared to healthy scaffolds. Collagens, proteoglycans, and ECM glycoproteins were... (More)

In idiopathic pulmonary fibrosis (IPF) structural properties of the extracellular matrix (ECM) are altered and influence cellular responses through cell-matrix interactions. Scaffolds (decellularized tissue) derived from subpleural healthy and IPF lungs were examined regarding biomechanical properties and ECM composition of proteins (the matrisome). Scaffolds were repopulated with healthy fibroblasts cultured under static stretch with heavy isotope amino acids (SILAC), to examine newly synthesized proteins over time. IPF scaffolds were characterized by increased tissue density, stiffness, ultimate force, and differential expressions of matrisome proteins compared to healthy scaffolds. Collagens, proteoglycans, and ECM glycoproteins were increased in IPF scaffolds, however while specific basement membrane (BM) proteins such as laminins and collagen IV were decreased, nidogen-2 was also increased. Findings were confirmed with histology, clearly showing a disorganized BM. Fibroblasts produced scaffold-specific proteins mimicking preexisting scaffold composition, where 11 out of 20 BM proteins were differentially expressed, along with increased periostin and proteoglycans production. We demonstrate how matrisome changes affect fibroblast activity using novel approaches to study temporal differences, where IPF scaffolds support a disorganized BM and upregulation of disease-associated proteins. These matrix-directed cellular responses emphasize the IPF matrisome and specifically the BM components as important factors for disease progression.

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published
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International Journal of Molecular Sciences
volume
20
issue
16
publisher
MOLECULAR DIVERSITY PRESERVATION INT
external identifiers
  • scopus:85071360531
  • pmid:31426504
ISSN
1422-0067
DOI
10.3390/ijms20164013
language
English
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yes
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5be649ac-c964-4c03-b385-98cd40c68b01
date added to LUP
2019-08-22 07:25:54
date last changed
2019-10-13 05:05:49
@article{5be649ac-c964-4c03-b385-98cd40c68b01,
  abstract     = {<p>In idiopathic pulmonary fibrosis (IPF) structural properties of the extracellular matrix (ECM) are altered and influence cellular responses through cell-matrix interactions. Scaffolds (decellularized tissue) derived from subpleural healthy and IPF lungs were examined regarding biomechanical properties and ECM composition of proteins (the matrisome). Scaffolds were repopulated with healthy fibroblasts cultured under static stretch with heavy isotope amino acids (SILAC), to examine newly synthesized proteins over time. IPF scaffolds were characterized by increased tissue density, stiffness, ultimate force, and differential expressions of matrisome proteins compared to healthy scaffolds. Collagens, proteoglycans, and ECM glycoproteins were increased in IPF scaffolds, however while specific basement membrane (BM) proteins such as laminins and collagen IV were decreased, nidogen-2 was also increased. Findings were confirmed with histology, clearly showing a disorganized BM. Fibroblasts produced scaffold-specific proteins mimicking preexisting scaffold composition, where 11 out of 20 BM proteins were differentially expressed, along with increased periostin and proteoglycans production. We demonstrate how matrisome changes affect fibroblast activity using novel approaches to study temporal differences, where IPF scaffolds support a disorganized BM and upregulation of disease-associated proteins. These matrix-directed cellular responses emphasize the IPF matrisome and specifically the BM components as important factors for disease progression.</p>},
  author       = {Elowsson Rendin, Linda and Löfdahl, Anna and Åhrman, Emma and Müller, Catharina and Notermans, Thomas and Michaliková, Barbora and Rosmark, Oskar and Zhou, Xiao-Hong and Dellgren, Göran and Silverborn, Martin and Bjermer, Leif and Malmström, Anders and Larsson-Callerfelt, Anna-Karin and Isaksson, Hanna and Malmström, Johan and Westergren-Thorsson, Gunilla},
  issn         = {1422-0067},
  language     = {eng},
  month        = {08},
  number       = {16},
  publisher    = {MOLECULAR DIVERSITY PRESERVATION INT},
  series       = {International Journal of Molecular Sciences},
  title        = {Matrisome Properties of Scaffolds Direct Fibroblasts in Idiopathic Pulmonary Fibrosis},
  url          = {http://dx.doi.org/10.3390/ijms20164013},
  doi          = {10.3390/ijms20164013},
  volume       = {20},
  year         = {2019},
}