Collagenase IV plays an important role in regulating hair cycle by inducing VEGF, IGF-1, and TGF-β expression.
Collagenase IV plays an important role in regulating hair cycle by inducing VEGF, IGF-1, and TGF-β expression.
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胶原酶IV通过诱导VEGF，IGF-1和TGF-β表达在调节头发周期中起重要作用。
DOI：
10.2147/dddt.s8912
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Hu ZQ
中科院分区：
文献类型：
--
作者：
Hou C;Miao Y;Wang J;Wang X;Chen CY;Hu ZQ
据报道，胶原酶（基质金属蛋白酶2 [MMP-2]和基质金属蛋白酶9 [MMP-9]）与毛发周期有关，而这种联系的机制在很大程度上是未知的。将小鼠随机分为四组：生理盐水和5、10和15 nM SB-3CT。免疫组化法检测MMP-2、MMP-9蛋白表达。采用实时荧光定量聚合酶链反应和酶联免疫吸附法检测VEGF、IGF-1、TGF-β和GAPDH的mRNA和蛋白水平。基于苏木精和伊红染色对生长期III-IV期生长的毛囊进行评分。还评估了毛发再生。结果表明，脱毛后各酶的mRNA表达量在毛发生长期后期有一个高峰，在休止期有一个低谷。免疫组化结果显示，MMP-2的最高表达量大于MMP-9，且在生长期内酶的最高表达量发生变化。MMP-2在生长期早期的分布由毛乳头、角质形成细胞束、外根鞘和基底板变为生长期晚期的毛球、内根鞘和外根鞘。MMP-9的定位在生长期早期从部分角质形成细胞转移到毛乳头，在生长期晚期转移到外根鞘。VEGF、IGF-1和TGF-β已被证明可调节毛发生长。结果发现，VEGF和IGF-1的mRNA和蛋白表达在生长期有一个高峰，在退化期和休止期下降。相反，TGF-β的mRNA和蛋白表达变化，最高和最低水平分别在生长期和休止期。使用胶原酶IV的选择性抑制剂SB-3CT，小鼠表现出显著的毛发生长抑制和VEGF、IGF-1和TGF-β的表达降低。MMPs激动剂还显著增加VEGF、IGF-1和TGF-β的表达。同时，SB-3CT处理显著抑制毛发生长。提示MMP-2和MMP-9在毛发生长周期中起重要作用，其作用可能与VEGF、IGF-1和TGF-β的诱导表达有关。
It has been reported that collagenases (matrix metalloproteinase 2 [MMP-2] and matrix metalloproteinase 9 [MMP-9]) are associated with hair cycle, whereas the mechanism of the association is largely unknown. The mice were randomly allocated into four groups: saline, and 5, 10, and 15 nM SB-3CT. Immunohistochemical analysis was employed to examine MMP-2 and MMP-9 protein. Real-time polymerase chain reaction and enzyme-linked immunosorbent assay were performed to determine mRNA and protein levels of VEGF, IGF-1, TGF-β, and GAPDH. Growing hair follicles from anagen phase III–IV were scored based on hematoxylin and eosin staining. Hair regrowth was also evaluated. Results showed that mRNA expressions of enzymes changed with a peak at late anagen and a trough at telogen after depilation. Immunostaining showed that the highest expression of MMP-2 was more than that of MMP-9, and the highest expression of enzymes changed during anagen. The localizations of MMP-2 changed from dermal papilla, keratinocyte strand, out of root sheath, and basal plate at early anagen, to hair bulb, inner root sheath, and outer root sheath at late anagen. The localization of MMP-9 changed from partial keratinocyte to dermal papilla at early anagen and to outer root sheath at late anagen. VEGF, IGF-1, and TGF-β have been shown to regulate hair growth. We found mRNA and protein expressions of VEGF and IGF-1 fluctuated with a peak at anagen and a decrease at catagen to telogen. In contrast, mRNA and protein expressions of TGF-β changed with highest and lowest levels at anagen and telogen, respectively. With selective inhibitor of collagenase IV, SB-3CT, mice showed significant suppressed hair growth and decreased expression of VEGF, IGF-1, and TGF-β. The MMPs agonist also significantly increased expression of VEGF, IGF-1, and TGF-β. Meanwhile, SB-3CT treatment significantly suppressed hair growth. All these data suggest that the type IV collagenases, MMP-2 and MMP-9, play important roles in hair cycle, and this could be mediated by induced expression of VEGF, IGF-1, and TGF-β.