Human skin culture as an ex vivo model for assessing the fibrotic effects of insulin-like growth factor binding proteins.
Human skin culture as an ex vivo model for assessing the fibrotic effects of insulin-like growth factor binding proteins.
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DOI：
10.2174/1874312900802010017
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Feghali-Bostwick CA
中科院分区：
文献类型：
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作者：
Yasuoka H;Larregina AT;Yamaguchi Y;Feghali-Bostwick CA
系统性硬化症（SSc）是一种病因不明的结缔组织疾病。 SSc 的一个标志是皮肤和内脏器官的纤维化。我们最近证明，SSc 患者皮肤成纤维细胞的原代培养物中 IGFBP-3 和 IGFBP-5 的表达增加。在体外，IGFBP-3和IGFBP-5诱导小鼠纤维化表型，IGFBP-5引发小鼠真皮纤维化。为了评估 IGFBP 引发纤维化的能力，我们使用了离体人体皮肤器官培养模型。我们的研究结果表明，IGFBP-3 和 IGFBP-5（而非 IGFBP-4）增加了人类皮肤外植体中的真皮和胶原束厚度，导致真皮明显纤维化和增厚。这些纤维化作用持续至少两周。我们的研究结果表明，离体人体皮肤是评估 IGFBP 等纤维化诱导因子的影响以及评估抑制剂/疗法阻止纤维化进展并可能逆转纤维化的功效的合适模型。
Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology. A hallmark of SSc is fibrosis of the skin and internal organs. We recently demonstrated increased expression of IGFBP-3 and IGFBP-5 in primary cultures of fibroblasts from the skin of patients with SSc. In vitro, IGFBP-3 and IGFBP-5 induced a fibrotic phenotype and IGFBP-5 triggered dermal fibrosis in mice. To assess the ability of IGFBPs to trigger fibrosis, we used an ex vivo human skin organ culture model. Our findings demonstrate that IGFBP-3 and IGFBP-5, but not IGFBP-4, increase dermal and collagen bundle thickness in human skin explants, resulting in substantial dermal fibrosis and thickening. These fibrotic effects were sustained for at least two weeks. Our findings demonstrate that human skin ex vivo is an appropriate model to assess the effects of fibrosis-inducing factors such as IGFBPs, and for evaluating the efficacy of inhibitors/therapies to halt the progression of fibrosis and potentially reverse it.