Knockdown of HIF-1 alpha inhibits the proliferation and migration of outer root sheath cells exposed to hypoxia in vitro: An involvement of Shh pathway

文献类型： 外文期刊

第一作者： Zhang, Haihua

作者： Zhang, Haihua;Song, Xingchao;Wang, Shiyong;Si, Huazhe;Li, Guangyu;Nan, Weixiao

作者机构：

关键词： Hair follicle;ORS cells;Proliferation;Migration;HIF-1 alpha;Shh signaling pathway

期刊名称：LIFE SCIENCES （ 影响因子：5.037； 五年影响因子：4.689 ）

ISSN： 0024-3205

年卷期： 2017 年 191 卷

页码：

收录情况： SCI

摘要： Aims: Outer root sheath (ORS) is a highly proliferative component of a hair follicle. This study is performed to investigate whether hypoxia-induced elevation of hypoxia-inducible factor (HIF)-1 alpha, a transcriptional activator, contributes to the outgrowth of ORS cells in vitro. Main methods: Hair follicles with intact ORS collected from 4-month old male American minks were cultured in normoxic or hypoxic condition (3% oxygen) for 7 days. Primary ORS cells isolated from the mink hair follicles were exposed to hypoxia for 12, 24 or 48 h, and their proliferation was analyzed with immunofluorescence assay using anti-proliferating cell nuclear antigen (PCNA) antibody. The migratory ability of ORS cells was detected via the transwell chamber. The endogenous HIF-1 alpha was knocked down with its specific siRNA in ORS cells. Key findings: Hypoxic exposure induced an elevation of HIF-1 alpha in ex vivo cultured hair follicles. The mRNA and protein levels of sonic hedgehog (Shh), Shh receptor Patched 1, Smoothened and glioma-associated oncogene homologue 1 were upregulated. In vitro, hypoxia induced an increase in HIF-1 alpha in ORS cells. Further, under hypoxic condition, the number of PCNA-positive cells was increased, and more cells migrated towards high serum media. Hypoxia-enhanced proliferation and migration of ORS cells were suppressed either by HIF-1 alpha siRNA or by pharmacological inhibitors of Shh pathway, cyclopamine and GANT61. The activation of Shh pathway was attenuated in HIF-1 alpha-silenced ORS cells under hypoxic condition. Significance: Our work demonstrates a direct role of activated HIF-1/Shh biological axis in sustaining the development of ORS in vitro.

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