Hair Loss Caused by Gain-of-Function Mutant TRPV3 Is Associated with Premature Differentiation of Follicular Keratinocytes.
Hair Loss Caused by Gain-of-Function Mutant TRPV3 Is Associated with Premature Differentiation of Follicular Keratinocytes.
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DOI：
10.1016/j.jid.2020.11.036
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Song Z;Chen X;Zhao Q;Stanic V;Lin Z;Yang S;Chen T;Chen J;Yang Y
TRPV3基因的功能获得性突变可导致Olmsted综合征，其特征为掌跖和掌周角化病、瘙痒和脱发。脱发的潜在机制仍不清楚。在这里，我们通过将点突变G568V引入小鼠中相应的Trpv3位点来工程化Olmsted综合征小鼠模型。这些小鼠发生完全渗透性脱发。脱发与毛囊角质形成细胞的过早分化有关，其特征在于透明质蛋白和角蛋白的过早变性、脱亚胺蛋白的产生增加、细胞凋亡增加以及已知调节毛囊分化的转录调节因子（Foxn 1、Msx 2、Dlx 3和Gata 3）的减弱。这些异常发生在内根鞘和毛干的内侧近端区域，其中Trpv3高度表达，并且与毛管和毛干的受损形成相关。突变Trpv3小鼠还表现出外根鞘增殖增加，毛发周期加快，毛囊干细胞减少，再生毛囊小型化。这项研究的结果表明，有丝分裂后滤泡角质形成细胞的早熟成熟导致奥姆斯特德综合征患者脱发。
Gain-of-function mutations in the TRPV3 gene can cause Olmsted syndrome characterized by palmoplantar and periorificial keratoderma, itch, and hair loss. The mechanism underlying hair loss remains unclear. Here, we engineered an Olmsted syndrome mouse model by introducing the point mutation G568V to the corresponding Trpv3 locus in mice. These mice developed fully penetrant hair loss. The hair loss was associated with premature differentiation of follicular keratinocytes characterized by precocious degeneration of trichohyalin and keratins, increased production of deiminated proteins, elevated apoptosis, and attenuation of transcription regulators (Foxn1, Msx2, Dlx3, and Gata3) known to regulate hair follicle differentiation. These abnormalities occurred in the medial-proximal region of the inner root sheath and the hair shaft, where Trpv3 is highly expressed, and correlated with impaired formation of the hair canal and the hair shaft. The mutant Trpv3 mice also exhibited increased proliferation in the outer root sheath, accelerated hair cycle, reduction of hair follicle stem cells, and miniaturization of regenerated hair follicles. Findings from this study suggest that precocious maturation of postmitotic follicular keratinocytes drives hair loss in Olmsted syndrome patients.
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影响因子：
6.5
作者：
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通讯作者：
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DOI：
10.1016/j.bbrc.2007.08.170
发表时间：
2007-11-23
影响因子：
3.1
作者：
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