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Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.

Andersson Sjöland, Annika LU ; Thiman, Lena LU ; Nihlberg, Kristian LU ; Hallgren, Oskar LU ; Rolandsson Enes, Sara LU ; Skog, Ingrid; Mared, Lena LU ; Hansson, Lennart LU ; Eriksson, Leif LU and Bjermer, Leif LU , et al. (2011) In The Journal of Heart and Lung Transplantation 30. p.945-954
Abstract
BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of... (More)
BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied. RESULTS: At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p < 0.01 p < 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p < 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function. CONCLUSIONS: LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS. (Less)
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Contribution to journal
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published
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in
The Journal of Heart and Lung Transplantation
volume
30
pages
945 - 954
publisher
Elsevier
external identifiers
  • wos:000293038800013
  • pmid:21624839
  • scopus:79959928362
ISSN
1557-3117
DOI
10.1016/j.healun.2011.04.006
language
English
LU publication?
yes
id
77b92b1b-6c5e-4c9f-9137-88a326cf31a4 (old id 2008676)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21624839?dopt=Abstract
date added to LUP
2011-07-01 11:56:10
date last changed
2017-07-30 04:48:27
@article{77b92b1b-6c5e-4c9f-9137-88a326cf31a4,
  abstract     = {BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied. RESULTS: At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p &lt; 0.01 p &lt; 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p &lt; 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function. CONCLUSIONS: LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS.},
  author       = {Andersson Sjöland, Annika and Thiman, Lena and Nihlberg, Kristian and Hallgren, Oskar and Rolandsson Enes, Sara and Skog, Ingrid and Mared, Lena and Hansson, Lennart and Eriksson, Leif and Bjermer, Leif and Westergren-Thorsson, Gunilla},
  issn         = {1557-3117},
  language     = {eng},
  pages        = {945--954},
  publisher    = {Elsevier},
  series       = {The Journal of Heart and Lung Transplantation},
  title        = {Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.},
  url          = {http://dx.doi.org/10.1016/j.healun.2011.04.006},
  volume       = {30},
  year         = {2011},
}