Ota Yutaka, Saitoh Yuko, Suzuki Satoshi, Ozawa Kazuo, Kawano Mitsuko, Imamura Toru
POLA Laboratories, POLA Chemical Institute Inc., 560 Kashio-cho, Totsuka-ku, Yokohama 244-0812, Japan.
Biochem Biophys Res Commun. 2002 Jan 11;290(1):169-76. doi: 10.1006/bbrc.2001.6140.
Fibroblast growth factor (FGF) 5 inhibits hair growth and induces catagen in mouse hair follicles, in vivo. Given that FGF-5 receptor (FGFR1) is expressed in dermal papilla cells (DPCs), which are known to stimulate outer root sheath cell (ORSC) proliferation, we hypothesized that FGF-5 attenuates DPC-mediated ORSC proliferation. In the present study, DPCs and ORSCs were isolated from rat vibrissae, after which the effects of FGF-5 on proliferation of ORSCs cultured in DPC-conditioned medium were assessed. We first confirmed that FGFR1 was expressed in cultured DPCs and detected FGFR2-4 as well. ORSC proliferation was increased approximately twofold when the cells were cultured in DPC-conditioned medium, and the effect was unaltered by FGF-5. In addition, FGF-5 did not directly inhibit ORSC proliferation; indeed, it actually promoted proliferation of both DPCs and ORSCs. When DPCs were first activated by exposure to FGF-1 and FGF-2, which are expressed in hair follicles during anagen, ORSC proliferation observed in the resultant conditioned medium was substantially greater than in medium conditioned by unstimulated DPCs. The FGF-1-induced enhancement was reversed by FGF-5, diminishing ORSC proliferation to control levels. By contrast, the enhancement of DPC-mediated ORSC proliferation by FGF-2 was not suppressed by FGF-5. Proliferation of ORSCs did not depend on DPC proliferation, nor did FGF-1 directly promote ORSC proliferation. Dermal papillae thus appear to require activation before they will efficiently stimulate hair growth, and FGF-5 appears to inhibit hair growth and induce catagen by blocking that activation.
成纤维细胞生长因子（FGF）5在体内可抑制小鼠毛囊的毛发生长并诱导其进入退行期。鉴于FGF - 5受体（FGFR1）在真皮乳头细胞（DPCs）中表达，而真皮乳头细胞已知可刺激外根鞘细胞（ORSCs）增殖，我们推测FGF - 5会减弱DPC介导的ORSCs增殖。在本研究中，从大鼠触须中分离出DPCs和ORSCs，之后评估FGF - 5对在DPC条件培养基中培养的ORSCs增殖的影响。我们首先证实FGFR1在培养的DPCs中表达，同时也检测到了FGFR2 - 4。当细胞在DPC条件培养基中培养时，ORSCs增殖增加了约两倍，且该效应不受FGF - 5影响。此外，FGF - 5并未直接抑制ORSCs增殖；实际上，它反而促进了DPCs和ORSCs两者的增殖。当DPCs首先通过暴露于生长期毛囊中表达的FGF - 1和FGF - 2而被激活时，在所得条件培养基中观察到的ORSCs增殖显著大于未受刺激的DPCs条件培养基中的增殖。FGF - 5可逆转FGF - 1诱导的增强作用，将ORSCs增殖降低至对照水平。相比之下，FGF - 2介导的DPC对ORSCs增殖的增强作用未被FGF - 5抑制。ORSCs的增殖不依赖于DPC的增殖，FGF - 1也未直接促进ORSCs增殖。因此，真皮乳头似乎需要先被激活才能有效刺激毛发生长，而FGF - 5似乎通过阻断这种激活来抑制毛发生长并诱导退行期。
