Heat shock protein B1-deficient mice display impaired wound healing.
There is large literature describing in vitro experiments on heat shock protein (hsp)B1 but understanding of its function in vivo is limited to studies in mice overexpressing human hspB1 protein. Experiments in cells have shown that hspB1 has chaperone activity, a cytoprotective role, regulates infl...
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doaj-5e0d1e534624428a84b6788f6b5660f12020-11-25T00:24:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7738310.1371/journal.pone.0077383Heat shock protein B1-deficient mice display impaired wound healing.Jonathan CroweAnna AubaredaKay McNameePaulina M PrzybycienXin LuRichard O WilliamsGeorge Bou-GhariosJeremy SaklatvalaJonathan L E DeanThere is large literature describing in vitro experiments on heat shock protein (hsp)B1 but understanding of its function in vivo is limited to studies in mice overexpressing human hspB1 protein. Experiments in cells have shown that hspB1 has chaperone activity, a cytoprotective role, regulates inflammatory gene expression, and drives cell proliferation. To investigate the function of the protein in vivo we generated hspB1-deficient mice. HspB1-deficient fibroblasts display increased expression of the pro-inflammatory cytokine, interleukin-6, compared to wild-type cells, but reduced proliferation. HspB1-deficient fibroblasts exhibit reduced entry into S phase and increased expression of cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1). The expression of hspB1 protein and mRNA is also controlled by the cell cycle. To investigate the physiological function of hspB1 in regulating inflammation and cell proliferation we used an excisional cutaneous wound healing model. There was a significant impairment in the rate of healing of wounds in hspB1-deficient mice, characterised by reduced re-epithelialisation and collagen deposition but also increased inflammation. HspB1 deficiency augments neutrophil infiltration in wounds, driven by increased chemokine (C-X-C motif) ligand 1 expression. This appears to be a general mechanism as similar results were obtained in the air-pouch and peritonitis models of acute inflammation.http://europepmc.org/articles/PMC3797036?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jonathan Crowe Anna Aubareda Kay McNamee Paulina M Przybycien Xin Lu Richard O Williams George Bou-Gharios Jeremy Saklatvala Jonathan L E Dean |
spellingShingle |
Jonathan Crowe Anna Aubareda Kay McNamee Paulina M Przybycien Xin Lu Richard O Williams George Bou-Gharios Jeremy Saklatvala Jonathan L E Dean Heat shock protein B1-deficient mice display impaired wound healing. PLoS ONE |
author_facet |
Jonathan Crowe Anna Aubareda Kay McNamee Paulina M Przybycien Xin Lu Richard O Williams George Bou-Gharios Jeremy Saklatvala Jonathan L E Dean |
author_sort |
Jonathan Crowe |
title |
Heat shock protein B1-deficient mice display impaired wound healing. |
title_short |
Heat shock protein B1-deficient mice display impaired wound healing. |
title_full |
Heat shock protein B1-deficient mice display impaired wound healing. |
title_fullStr |
Heat shock protein B1-deficient mice display impaired wound healing. |
title_full_unstemmed |
Heat shock protein B1-deficient mice display impaired wound healing. |
title_sort |
heat shock protein b1-deficient mice display impaired wound healing. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
There is large literature describing in vitro experiments on heat shock protein (hsp)B1 but understanding of its function in vivo is limited to studies in mice overexpressing human hspB1 protein. Experiments in cells have shown that hspB1 has chaperone activity, a cytoprotective role, regulates inflammatory gene expression, and drives cell proliferation. To investigate the function of the protein in vivo we generated hspB1-deficient mice. HspB1-deficient fibroblasts display increased expression of the pro-inflammatory cytokine, interleukin-6, compared to wild-type cells, but reduced proliferation. HspB1-deficient fibroblasts exhibit reduced entry into S phase and increased expression of cyclin-dependent kinase inhibitors p27(kip1) and p21(waf1). The expression of hspB1 protein and mRNA is also controlled by the cell cycle. To investigate the physiological function of hspB1 in regulating inflammation and cell proliferation we used an excisional cutaneous wound healing model. There was a significant impairment in the rate of healing of wounds in hspB1-deficient mice, characterised by reduced re-epithelialisation and collagen deposition but also increased inflammation. HspB1 deficiency augments neutrophil infiltration in wounds, driven by increased chemokine (C-X-C motif) ligand 1 expression. This appears to be a general mechanism as similar results were obtained in the air-pouch and peritonitis models of acute inflammation. |
url |
http://europepmc.org/articles/PMC3797036?pdf=render |
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