New roles for glial cell line-derived neurotrophic factor and neurturin -: Involvement in hair cycle control
New roles for glial cell line-derived neurotrophic factor and neurturin -: Involvement in hair cycle control
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DOI：
10.1016/s0002-9440(10)64972-3
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发表时间：
2000-03-01
影响因子：
6
通讯作者：
Paus, R
中科院分区：
文献类型：
--
作者：
Botchkareva, NV;Botchkarev, VA;Paus, R
胶质细胞源性神经营养因子（GDNF），神经营养素（NTN），及其受体，GDNF家族受体α-1。(GFRα-1）和GDNF家族受体α-2（GFR α-2）对肾脏和神经系统发育至关重要。然而，它们在皮肤生物学中的作用，特别是在毛发生长控制中的作用，还不清楚。我们研究了GDNF、neurturin、GFR α-1和GFR α-2在小鼠皮肤中的表达和功能，在毛囊（HF）从静止状态（休止期）到活跃生长（生长期），然后通过回归（退化期）回到休止期的周期性转化过程中。GDNF蛋白和GFR α-1信使RNA在休止期皮肤中显著表达，其缺乏NTN和GFR α-2转录物。早期生长期发育伴随着GDNF蛋白和GFR α-1转录物的皮肤含量的显著下降。在生长期-退化期过渡期间，GDNF、GFR α-1、NTN和GFR α-2转录物达到最高水平。与野生型对照相比，GFR α-1（+/-）和GFR α-2（-/-）敲除小鼠显示出明显加速的退行期发育。此外，GDNF或NTN给药显著延缓器官培养的小鼠皮肤中的HF消退。这表明GDNF/GFR α-1和NTN/GFR α-2信号传导在皮肤生物学中的重要的、先前未被认识的作用，特别是在控制脱发驱动的HF退化中，并提高了GFR α-1/GFR α-2激动剂/拮抗剂可能用于治疗与退行期发育异常相关的毛发生长障碍的可能性。
Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN), and their receptors, GDNF family receptor alpha-1. (GFR alpha-1) and GDNF family receptor alpha-2 (GFR alpha-2), are critically important for kidney and nervous system development. However, their role in skin biology, specifically in hair growth control, is as yet unknown. We have studied expression and function of GDNF, neurturin, GFR alpha-1, and GFR alpha-2 in murine skin during the cyclic transformation of the hair follicle (HF) from its resting state (telogen) to active growth (anagen) and then through regression (catagen) back to telogen. GDNF protein and GFR alpha-1 messenger RNA are prominently expressed in telogen skin, which lacks NTN and GFR alpha-2 transcripts. Early anagen development is accompanied by a significant decline in the skin content of GDNF protein and GFR alpha-1 transcripts. During the anagen-catagen transition, GDNF, GFR alpha-1, NTN, and GFR alpha-2 transcripts reach maximal levels. Compared with wild-type controls, GFR alpha-1 (+/-) and GFR alpha-2 (-/-) knockout mice show a significantly accelerated catagen development. Furthermore, GDNF or NTN administration significantly retards HF regression in organ-cultured mouse skin. This suggests important, previously unrecognized roles for GDNF/GFR alpha-1 and NTN/GFR alpha-2 signaling in skin biology, specifically in the control of apoptosis-driven HF involution, and raises the possibility that GFR alpha-1/GFR alpha-2 agonists/antagonists might become exploitable for the treatment of hair growth disorders that are related to abnormalities in catagen development.