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...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2013
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| _version_ | 1797067952968695808 |
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| author | Crowe, J Aubareda, A McNamee, K Przybycien, P Lu, X Williams, R Bou-Gharios, G Saklatvala, J Dean, J |
| author_facet | Crowe, J Aubareda, A McNamee, K Przybycien, P Lu, X Williams, R Bou-Gharios, G Saklatvala, J Dean, J |
| author_sort | Crowe, J |
| collection | OXFORD |
| 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 p27kip1 and p21waf1. 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. |
| first_indexed | 2024-03-06T22:03:47Z |
| format | Journal article |
| id | oxford-uuid:4f78ea82-ac21-44d4-bed7-fcf44ded2938 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:03:47Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:4f78ea82-ac21-44d4-bed7-fcf44ded29382022-03-26T16:07:24ZHeat shock protein B1-deficient mice display impaired wound healingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4f78ea82-ac21-44d4-bed7-fcf44ded2938EnglishSymplectic Elements at OxfordPublic Library of Science2013Crowe, JAubareda, AMcNamee, KPrzybycien, PLu, XWilliams, RBou-Gharios, GSaklatvala, JDean, JThere 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 p27kip1 and p21waf1. 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. |
| spellingShingle | Crowe, J Aubareda, A McNamee, K Przybycien, P Lu, X Williams, R Bou-Gharios, G Saklatvala, J Dean, J Heat shock protein B1-deficient mice display impaired wound healing |
| title | 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_short | Heat shock protein B1-deficient mice display impaired wound healing |
| title_sort | heat shock protein b1 deficient mice display impaired wound healing |
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