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.
BACKGROUND AND PURPOSE: Distinguishing schwannomas from paragangliomas in the head and neck and determining succinate dehydrogenase (SDH) mutation status in paragangliomas are clinically important. We aimed to assess the clinical usefulness of DWI and dynamic contrast-enhanced MR imaging in differentiating these 2 types of tumors, as well as the SDH mutation status of paragangliomas. MATERIALS AND METHODS:This retrospective study from June 2016 to June 2020 included 42 patients with 15 schwannomas and 27 paragangliomas (10 SDH mutation-positive and 17 SDH mutation-negative). ADC values, dynamic contrast-enhanced MRI parameters, and tumor imaging characteristics were compared between the 2 tumors and between the mutation statuses of paragangliomas as appropriate. Multivariate stepwise logistic regression analysis was performed to identify significant differences in these parameters.RESULTS: Fractional plasma volume (P # .001), rate transfer constant (P ¼ .038), time-to-maximum enhancement (P , .001), maximum signal-enhancement ratio (P , .001) and maximum concentration of contrast agent (P , .001), velocity of enhancement (P ¼ .002), and tumor characteristics including the presence of flow voids (P ¼ .001) and enhancement patterns (P ¼ .027) showed significant differences between schwannomas and paragangliomas, though there was no significant difference in ADC values. In the multivariate logistic regression analysis, fractional plasma volume was identified as the most significant value for differentiation of the 2 tumor types (P ¼ .014). ADC values were significantly higher in nonhereditary than in hereditary paragangliomas, while there was no difference in dynamic contrast-enhanced MR imaging parameters.CONCLUSIONS: Dynamic contrast-enhanced MR imaging parameters show promise in differentiating head and neck schwannomas and paragangliomas, while DWI can be useful in detecting SDH mutation status in paragangliomas. ABBREVIATIONS: AUC ¼ area under the curve; DCE ¼ dynamic contrast-enhanced; EES ¼ extravascular extracellular space; Kep ¼ rate transfer constant between EES and blood plasma per minute; K trans ¼ volume transfer constant between EES and blood plasma per minute; SDH ¼ succinate dehydrogenase; SER ¼ signal-enhancement ratio; TIC ¼ time-intensity curve; TME ¼ time-to-maximum enhancement; Ve ¼ EES volume per unit tissue volume; Vp ¼ blood plasma volume per unit tissue volume
This study further delineates the profile of RON. Visual loss is often acute, profound, and monocular but may decline slowly after acute onset and later affect both optic nerves. High-resolution MRI of the optic nerves usually will display enhancement of a discrete segment of the intracranial prechiasmatic optic nerve, often with accompanying expansion and T2 hyperintensity. In some cases, these imaging features may precede vision loss. They may be subtle or appear after vision loss. Enhancement lingers for a wide interval, ranging in this study from 2 to at least 17 months. Recognition of these imaging characteristics assists in confirmation of the diagnosis of RON.
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