Laminin-511, inducer of hair growth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia.

Laminin-511, inducer of hair growth, is down-regulated and its suppressor in hair growth, laminin-332 up-regulated in chemotherapy-induced alopecia.
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DOI:
10.1016/j.jdermsci.2010.02.005
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发表时间:
2010-04
影响因子:
4.6
通讯作者:
Kobayashi H
Kobayashi H
中科院分区:
医学3区
文献类型:
--
作者:
Imanishi H;Tsuruta D;Tateishi C;Sugawara K;Paus R;Tsuji T;Ishii M;Ikeda K;Kunimoto H;Nakajima K;Jones JC;Kobayashi H

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化疗引起的脱发(CIA)具有破坏性的美容效果,尤其是对于年轻人。最近的数据表明,皮肤的两种主要基底膜成分(层粘连蛋白-332 和-511)对毛发生长具有相反的作用。在这项研究中,我们研究了层粘连蛋白-332 和-511 在 CIA 中的作用和定位。我们检测了环磷酰胺 (CYP) 治疗 C57BL/6 小鼠诱导的 CIA 营养不良退行期期间层粘连蛋白-332 和 -511 的表达。我们的数据表明,在 CIA 毛囊下三分之一的外根鞘 (ORS) 周围营养不良的退行期中晚期后,层粘连蛋白 332 及其受体 α6β4 整合素均上调(定量和空间上)。这种上调也发生在转录水平。相比之下,层粘连蛋白 511 在营养不良中期后在蛋白质水平上下调,层粘连蛋白 511 的转录失活在表皮和 ORS 角质形成细胞中在营养不良中期早期短暂发生。 Laminin-511 表达与 CIA 中 α3 整合素的表达相关,我们还证明 Laminin-511 可以上调培养的角质形成细胞中 α3 整合素启动子的活性。在小鼠背部皮肤注射富含层粘连蛋白 511 的蛋白质提取物(而非重组层粘连蛋白 332)可延缓 CYP 诱导的 CIA 脱发。我们认为 CIA 的突然脱发至少部分是由转录和翻译水平上层粘连蛋白 511 的下调和层粘连蛋白 332 的上调引起的。
Chemotherapy-induced alopecia (CIA) has a devastating cosmetic effect, especially in the young. Recent data indicate that two major basement membrane components (laminin-332 and -511) of the skin have opposing effects on hair growth. In this study, we examined the role and localization of laminin-332 and -511 in CIA. We examined the expression of laminin-332 and -511 during the dystrophic catagen form of CIA induced in C57BL/6 mice by cyclophosphamide (CYP) treatment. Our data indicate that both laminin-332 and its receptor α6β4 integrin are up-regulated (both quantitatively and spatially) after mid to late dystrophic catagen around the outer root sheath (ORS) in the lower third of hair follicles in CIA. This up-regulation also occurs at the transcriptional level. In contrast, laminin-511 is down-regulated after mid dystrophic catagen at the protein level, with transcriptional inactivation of laminin-511 occurring transiently at the early dystrophic catagen stage in both epidermal and ORS keratinocytes. Laminin-511 expression correlates with expression of α3 integrin in CIA and we also demonstrate that laminin-511 can up-regulate the activity of the α3 integrin promoter in cultured keratinocytes. Injection of a laminin-511 rich protein extract, but not recombinant laminin-332, in the back skin of mice delays hair loss in CYP-induced CIA. We propose that abrupt hair loss in CIA is, at least in part, caused by down-regulation of laminin-511 and up-regulation of laminin-332 at the transcriptional and translational levels.
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