PMID- 16691201 OWN - NLM STAT- MEDLINE DCOM- 20060905 LR - 20161124 IS - 0022-202X (Print) IS - 0022-202X (Linking) VI - 126 IP - 8 DP - 2006 Aug TI - Diminished induction of skin fibrosis in mice with MCP-1 deficiency. PG - 1900-8 AB - Scar and fibrosis are often the end result of mechanical injury and inflammatory diseases. One chemokine that is repeatedly linked to fibrotic responses is monocyte chemoattractant protein-1 (MCP-1). We utilized a murine fibrosis model that produces dermal lesions similar to scleroderma to evaluate collagen fibrillogenesis in the absence of MCP-1. Dermal fibrosis was induced by subcutaneous injection of bleomycin into the dorsal skin of MCP-1-/- and wild-type C57BL/6 mice. After 4 weeks of daily injections, bleomycin treatment led to thickened collagen bundles with robust inflammation in the lesional dermis of wild-type mice. In contrast, the lesional skin of MCP-1-/- mice exhibited a dermal architecture similar to phosphate-buffered saline (PBS)-injected control and normal skin, with few inflammatory cells. Ultrastructural analysis of the lesional dermis from bleomycin-injected wild-type mice revealed markedly abnormal arrangement of collagen fibrils, with normal large diameter collagen fibrils replaced by small collagen fibrils of 41.5 nm. In comparison, the dermis of bleomycin-injected MCP-1-/- mice displayed a uniform pattern of fibril diameters that was similar to normal skin (average diameter 76.7 nm). The findings implicate MCP-1 as a key determinant in the development of skin fibrosis induced by bleomycin, and suggest that MCP-1 may influence collagen fiber formation in vivo. FAU - Ferreira, Ahalia M AU - Ferreira AM AD - Department of Surgery, The Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois, USA. FAU - Takagawa, Shinsuke AU - Takagawa S FAU - Fresco, Raoul AU - Fresco R FAU - Zhu, Xiaofeng AU - Zhu X FAU - Varga, John AU - Varga J FAU - DiPietro, Luisa A AU - DiPietro LA LA - eng GR - R01GM55238/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060511 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Collagen Type I) RN - 0 (Dcn protein, mouse) RN - 0 (Decorin) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Fmod protein, mouse) RN - 0 (HSP47 Heat-Shock Proteins) RN - 0 (Proteoglycans) RN - 0 (Serpinh1 protein, mouse) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 11056-06-7 (Bleomycin) RN - 126468-95-9 (Fibromodulin) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Mmp13 protein, mouse) SB - IM MH - Animals MH - Antimetabolites, Antineoplastic MH - Bleomycin MH - Chemokine CCL2/deficiency/*genetics/metabolism MH - Collagen Type I/genetics/metabolism/ultrastructure MH - Collagenases/metabolism MH - Decorin MH - Dermis/*pathology/physiopathology MH - Disease Models, Animal MH - Extracellular Matrix Proteins/genetics MH - Fibroblasts/pathology/ultrastructure MH - Fibromodulin MH - Fibrosis MH - Gene Expression MH - HSP47 Heat-Shock Proteins/genetics MH - Matrix Metalloproteinase 13 MH - Mice MH - Mice, Inbred C57BL MH - Mice, Mutant Strains MH - Proteoglycans/genetics MH - Skin Diseases/chemically induced/*pathology/*physiopathology MH - Tissue Inhibitor of Metalloproteinases/metabolism MH - Transforming Growth Factor beta/metabolism MH - Transforming Growth Factor beta1 EDAT- 2006/05/13 09:00 MHDA- 2006/09/06 09:00 CRDT- 2006/05/13 09:00 PHST- 2006/05/13 09:00 [pubmed] PHST- 2006/09/06 09:00 [medline] PHST- 2006/05/13 09:00 [entrez] AID - S0022-202X(15)33003-7 [pii] AID - 10.1038/sj.jid.5700302 [doi] PST - ppublish SO - J Invest Dermatol. 2006 Aug;126(8):1900-8. doi: 10.1038/sj.jid.5700302. Epub 2006 May 11.