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.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-015-0198-5) contains supplementary material, which is available to authorized users.
Highlights
Human skin is the largest organ of the human body, and is composed mainly of two layers: the epidermis and the dermis
Double immunostaining for stromal cell-derived factor-1 (SDF-1) and heat shock protein 47 (HSP47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin
Double immunostaining for SDF-1 and HSP47, a marker of fibroblasts, revealed co-localization indicating that the majority of SDF-1 positive cells were dermal fibroblasts (Fig. 1B)
Summary
Human skin is the largest organ of the human body, and is composed mainly of two layers: the epidermis (outermost layer) and the dermis (vascular connective tissue below the epidermis). The epidermis is primarily composed of keratinocytes and the dermis is composed of a dense collagenrich extracellular matrix (ECM) and stromal cells such as fibroblasts. In human skin the dermis provides the structural and mechanical properties of the skin (Uitto, 1986), and intimately interacts with the epidermis to maintain skin homeostasis (Maas-Szabowski et al, 1999; Tuan et al, 1994). Stromal cells such as dermal fibroblasts provide a crucial microenvironment for epidermal keratinocyte function (Blanpain and Fuchs, 2009). Not much is known about the molecular details and the factors responsible for such complex interactions between dermal stromal cells and epidermal keratinocytes in both physiologic and pathologic conditions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
