title: Dermal fibroblast expression of stromal cell-derived factor-1 (SDF-1) promotes epidermal keratinocyte proliferation in normal and diseased skin.
abstract: Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled quantitative real-time RT-PCR revealed that SDF-1 is constitutively and predominantly expressed in dermal stromal cells in normal human skin in vivo. To our surprise, an extremely high level of SDF-1 transcription was observed in the dermis of normal human skin in vivo, evidenced by much higher mRNA expression level than type I collagen, the most abundant and highly expressed protein in human skin. SDF-1 was also upregulated in the tissues of many human skin disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein 47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1 activates the ERK (extracellular-signal-regulated kinases) pathway and functions as a mitogen to stimulate epidermal keratinocyte proliferation. Both overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the skin equivalent cultures significantly increased the number of keratinocyte layers and epidermal thickness. Conversely, the stimulative function of SDF-1 on keratinocyte proliferation was nearly completely eliminated by interfering with CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts. Our data reveal that extremely high levels of SDF-1 provide a crucial microenvironment for epidermal keratinocyte proliferation in both physiologic and pathologic skin conditions.
authors: Department of Pathology, Affiliated Hospital of Yanbian University, Yanji, 133000, China.
authors: Chunji
authors: C
authors: Quan
authors: Department of Dermatology, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.
authors: Moon Kyun
authors: MK
authors: Cho
authors: Hollings Cancer Center Biorepository and Tissue Analysis Resource, Medical University of South Carolina, Charleston, SC, 29425, USA.
authors: Yuan
authors: Y
authors: Shao
authors: Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors: Laurel E
authors: LE
authors: Mianecki
authors: Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors: Eric
authors: E
authors: Liao
authors: Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
authors: Daniel
authors: D
authors: Perry
authors: Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA. thquan@umich.edu.
authors: Taihao
authors: T
authors: Quan
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000235:genetics*; D000078404:Epidermal Cells; D004817:Epidermis / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000473:pathology*; D015398:Signal Transduction; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology
chemical_list: D054377:Chemokine CXCL12; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: SDF-1; dermal fibroblast; keratinocyte; proliferation; psoriasis; skin cancer