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Publication : The Role of Fibroblast Growth Factor-Binding Protein 1 in Skin Carcinogenesis and Inflammation.

First Author  Schmidt MO Year  2018
Journal  J Invest Dermatol Volume  138
Issue  1 Pages  179-188
PubMed ID  28864076 Mgi Jnum  J:251763
Mgi Id  MGI:6102438 Doi  10.1016/j.jid.2017.07.847
Citation  Schmidt MO, et al. (2018) The Role of Fibroblast Growth Factor-Binding Protein 1 in Skin Carcinogenesis and Inflammation. J Invest Dermatol 138(1):179-188
abstractText  Fibroblast growth factor-binding protein 1 (FGFBP1) is a secreted chaperone that mobilizes paracrine-acting FGFs, stored in the extracellular matrix, and presents them to their cognate receptors. FGFBP1 enhances FGF signaling including angiogenesis during cancer progression and is upregulated in various cancers. Here we evaluated the contribution of endogenous FGFBP1 to a wide range of organ functions as well as to skin pathologies using Fgfbp1-knockout mice. Relative to wild-type littermates, knockout mice showed no gross pathologies. Still, in knockout mice a significant thickening of the epidermis associated with a decreased transepidermal water loss and increased proinflammatory gene expression in the skin was detected. Also, skin carcinogen challenge by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate resulted in delayed and reduced papillomatosis in knockout mice. This was paralleled by delayed healing of skin wounds and reduced angiogenic sprouting in subcutaneous matrigel plugs. Heterozygous green fluorescent protein (GFP)-knock-in mice revealed rapid induction of gene expression during papilloma induction and during wound healing. Examination of wild-type skin grafted onto Fgfbp1 GFP-knock-in reporter hosts and bone marrow transplants from the GFP-reporter model into wild-type hosts revealed that circulating Fgfbp1-expressing cells migrate into healing wounds. We conclude that tissue-resident and circulating Fgfbp1-expressing cells modulate skin carcinogenesis and inflammation.
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