Increased severity of bleomycin-induced skin fibrosis in mice with leukocyte-specific protein 1 deficiency.
Fibrosis is a complex process resulting from persistent inflammation following tissue damage. It involves the interaction of numerous cell types, soluble mediators, and extracellular matrix. Recently, a newly identified cell type, the fibrocyte, has been reported to contribute to wound healing and to fibrotic conditions such as hypertrophic scarring. Previously, we established leukocyte-specific protein 1 (LSP1) as a new marker for fibrocytes. In the present study, we examined the biological role of LSP1 in the development of skin fibrosis using bleomycin in an Lsp1(-/-) mice. These animals showed a significant increase in fibrosis, with increased thickness of the skin and collagen content. The skin in Lsp1(-/-) mice injected with bleomycin had higher densities of neutrophils, macrophages, and fibrocytes. In accordance with the increased leukocyte infiltration, the expression levels of macrophage-derived chemokines, transforming growth factor-beta1, and connective tissue growth factor were all upregulated in Lsp1(-/-) mice. These results demonstrate that the absence of LSP1 promotes fibrosis in the skin. The most likely mechanism for this effect seems to be through an increase in leukocyte infiltration, leading to locally elevated synthesis and the release of chemokines and growth factors.
Wang
Jianfei
J
Wound Healing Research Group, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
Jiao
Haiyan
H
Stewart
Tara L
TL
Shankowsky
Heather A
HA
Scott
Paul G
PG
Tredget
Edward E
EE
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D001798:Blood Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D047908:Intracellular Signaling Peptides and Proteins; D007962:Leukocytes / Q000166:cytology; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D001798:Blood Proteins; C526318:CCN2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C490562:Lst1 protein, mouse; D008565:Membrane Proteins; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D055513:Connective Tissue Growth Factor