title: Heat shock protein B1-deficient mice display impaired wound healing.
abstract: 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.
authors.affiliation: Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Crowe
authors.forename: Anna
authors.initials: A
authors.lastname: Aubareda
authors.forename: Kay
authors.initials: K
authors.lastname: McNamee
authors.forename: Paulina M
authors.initials: PM
authors.lastname: Przybycien
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Richard O
authors.initials: RO
authors.lastname: Williams
authors.forename: George
authors.initials: G
authors.lastname: Bou-Gharios
authors.forename: Jeremy
authors.initials: J
authors.lastname: Saklatvala
authors.forename: Jonathan L E
authors.initials: JL
authors.lastname: Dean
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000172:deficiency* / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing; D015054:Zymosan / Q000009:adverse effects
chemical_list: D055551:HSP27 Heat-Shock Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D003094:Collagen; D015054:Zymosan