Department of Dermatology, University of Michigan, Medical Science Building I, Rm 6447, 1301 E. Catherine, Ann Arbor, MI, 48109, USA,
J Cell Commun Signal. 2011 Mar;5(1):69-80. doi: 10.1007/s12079-010-0114-y. Epub 2011 Jan 11.
CCN proteins are important modulators of development and function of adult organs. In this study, we examined the localization and expression of the six CCN family members in normal adult human skin and during wound healing in vivo. Transcript and protein expression were studied by laser-capture microdissection-coupled real-time PCR and immunohistochemistry, respectively. Our results demonstrate that CCN1, CCN4, and CCN6 are expressed at relatively low levels in normal human skin. CCN2, CCN3, and CCN5 are the most highly expressed transcripts in the epidermis. CCN3 and CCN5 proteins are prominent in epidermal keratinocytes, whereas CCN2 is primarily expressed in melanocytes. Differential expression within epidermal layers suggests that CCN3 and CCN5 are linked with keratinocyte differentiation. CCN2, CCN3 and CCN5, are the three most highly expressed transcripts in the dermis. Their respective proteins are produced to various extents by dermal fibroblasts, blood vessels, eccrine sweat glands and hair follicles. We find that most CCN family members are temporally and specifically regulated during different phases (inflammation, proliferation, and remodeling) of partial thickness wound repair. By highlighting spatial-temporal regulations of CCN family member expression in relation to cell proliferation and differentiation, our results suggest a diverse range of functions for CCN proteins in both epidermal and dermal cells, and provides a solid reference for interpretation of future studies aimed at understanding the role of CCN proteins in human skin physiology and diseases.
CCN 蛋白是成人器官发育和功能的重要调节因子。本研究通过激光捕获显微切割结合实时 PCR 和免疫组织化学，分别检测了 6 种 CCN 家族成员在正常成人皮肤和体内伤口愈合过程中的定位和表达。结果表明，CCN1、CCN4 和 CCN6 在正常皮肤中的表达水平相对较低。CCN2、CCN3 和 CCN5 在表皮中表达水平最高。CCN3 和 CCN5 蛋白在表皮角质形成细胞中表达显著，而 CCN2 主要在黑素细胞中表达。表皮各层的差异表达表明 CCN3 和 CCN5 与角质形成细胞分化有关。CCN2、CCN3 和 CCN5 是真皮中表达水平最高的三种转录本。它们各自的蛋白由真皮成纤维细胞、血管、小汗腺和毛囊不同程度地产生。我们发现，在部分厚度伤口修复的不同阶段（炎症、增殖和重塑），大多数 CCN 家族成员的表达具有时间和特异性。我们的研究结果表明，CCN 蛋白在表皮和真皮细胞中具有多种功能，为解释未来旨在了解 CCN 蛋白在人类皮肤生理和疾病中的作用的研究提供了可靠的参考，突出了 CCN 家族成员表达与细胞增殖和分化的时空调节。
