MicroRNA-370-5p inhibits pigmentation and cell proliferation by downregulating mitogen-activated protein kinase kinase kinase 8 expression in sheep melanocytes

In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.

Direct Transplant of Melanocytes from Normal Donor Area into Vitiligenous Recipient Area by Intralesional Injection of Melanocytes Using Spade Like Needle Technique

Background: Vitiligo is a common autoimmune inflammatory skin disease, where there are different surgical techniques for treatment of stable patches of vitiligo .Objective: To find non-costly, minimally invasive, simple technique by direct melanocytes transplant by spade needle technique in treatment of vitiligo. Patients and Methods: This interventional, therapeutic, comparative study was done in Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq from April 2014-March 2015. Twenty patients with localized, generalized and segmental vitiligo were included. Full history and examination for each patient was done with 4 (20%) males and 16 (80%) females and their ages ranged from 9 - 40 (23.15 ± 11.44) years. Forty one patches in 20 patients treated by spade grafting technique and the donor and recipient sites were demarcated and anesthesia done by xylocaine 2% with adrenalin 1:100,000. Transplantation was started by using disposable needle gauge 18 (the sharp end of needle was cut by a scissor to make it a spade like) with medical syringe 5 ml supplied with normal saline. The micro-pieces were taken from donor site and transplanted directly, easily and rapidly into dermis of recipient site and followed by pushing normal saline and the procedure was repeated to cover all recipient sites with 5 mm distance between injection points. The surface area of the lesions was calculated and the reduction rate was estimated every month till the end of the 4th month period of the treatment. Results: Including 41 patches in 20 patients with the surface area of the patches ranged from 1.5 - 90 cm2 (13.78 ± 17.57) cm2. The mean ±SD of surface area of lesions was decreased from 13.78 ± 17.57 cm2 at baseline visit to 13.61 ± 17.48 cm2 at the second visit (after 2 weeks ) which was statistically significant (p value ≤ 0.001). The mean surface area continued to be reduced till reaching 12.20 ± 15.68 cm2 at the third visit and 12.01 ± 15.55 cm2 at the fourth visit. All were statistically significant when compared to baseline visit. There was reduction in surface area 1.1% at two weeks, 9.93%, and 12.5% at the 2nd, 4th months respectively. Conclusions: Intradermal injection of melanocytes in patients with vitiligo by spade like needle was very quick and simple non-costly technique, and gave 12.5% reduction which could be repeated at different times until satisfactory re-pigmentation of vitiligenous skin is achieved.

Effect of Xiaobailing Decoction on Melanocytes in Vitro

Objective: To observe the effect of Xiaobailing Decoction(消白灵汤)on murine melanocytes in vitro and to explore the mechanism of Xiaobailing Decoction in the treatment of vitiligo. Methods: B-16F10 murine melanoma cells were cultured in 1640 medium and treated respectively with different concentrations (1mg/ml, 2mg/ml, 3mg/ml) of the Chinese drug Xiaobailing Decoction and its main components, the drugs for replenishing the kidney-yang, and the drugs for nourishing blood and activating blood circulation, etc. for 7 days. MMT assay was used to determine the proliferation of B-16F10 murine melanoma cells. NaOH cleavage assay was adopted to measure the melanogenesis of melanocytes. Results: Xiaobailing Decoction, the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation at different concentrations significantly improved the proliferation of B-16F10 murine melanoma cells from the 3rd day to the 5th day (P<0.05), with Xiaobailing Decoction at the concentrations of 1mg/ml having the most distinct action on promoting the proliferation of melanocytes on the 3rd day (P<0.001); And the drugs for replenishing the kidney-yang at the concentrations of 2mg/ml and 3mg/ml and the drugs for nourishing blood and activating blood circulation at 3mg/ml significantly increased melanogenesis of melanocytes (P<0.05). Conclusion: Xiaobailing Decoction can promote melanocytic proliferation and melanogenesis in vitro, and it is indicated that the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation play an important role in treating vitiligo.

Depigmentory Effects of Keishibukuryogankayokuinin in Human Epidermal Melanocytes

Keishibukuryogankayokuinin (KBY) is a traditional Japanese herbal medicine widely used to treat skin pigmentation. The scientific basis for its use is, however, unclear, and studies evaluating its mechanism and effectiveness are sparse. In this study, we compared the tyrosinase inhibitory effects of KBY and Keishibukuryogan (KB, which has the same composition of KBY, except Coix Seed [CS]) and CS under exposure to UV radiation as well as under non-exposure conditions. Neonatal human epidermal melanocytes obtained from a darkly pigmented donor were used. These cells were cultured in a final concentration of 500 μg/ml or 1000 μg/ml, to which KBY, KB, and CS were added. After incubation for 72 h, cells were stained with Fontana-Masson stain and counted. Tyrosinase activity was measured by its dopa oxidase activity, and tyrosinase expression was estimated using real-time PCR. For UV radiation, cells were exposed to UVB radiation for 90 s per day for 3 days. Under non-exposure conditions, tyrosinase activity significantly increased with both KBY and KB but significantly decreased with CS, regardless of the concentration. In addition, tyrosinase expression significantly decreased but only with KBY at both concentrations. Under UV radiation exposure, tyrosinase activity significantly increased with KBY and KB at both concentrations while tyrosinase expression significantly decreased with KBY and KB;a significant increase was, however, observed with CS at both concentrations. These results suggest that taking KBY after sunburn is effective against skin pigmentation, and the combination of KB and CS is useful for skin depigmentation.

THE EFFECT OF Ge-132 ON ULTRASTRUCTURE OF CULTURED MELANOCYTES

Objective To elucidate the effect of Ge 132 on the growth of melanocytes.Methods Melanocyes from epidermis were cultured and purified;the second generation of the cell was used for study;the cells were divided into two groups randomly,to group A, Ge 132 was added to the media at 0.04mg/L;to group B,common culturing method was used without Ge 132.After 5d, the cells were seperated by digestion for study by transmission electronic microscope.Results Compared to group B, the vaculoes of the cells were increased,mitochondria distended, endoplasmic reticulum dilated and the number of melanosome declined in the group A.Conclusion Ge 132 can inhibit the melanocytes growth at a certain concentration and might be used for treating pigmented diseases.

Ultrastructure of Amelanotic Melanocytes from Human Hair Follicles

To investigate the ultra structure of amelanotic melanocytes （AMMC）. Methods： The hair follicles obtained from normal human scalp by 0.50% collagenase type V treatment were washed with 0.1 mol/L phosphate buffer salt （PBS）. Hair-follicle cell suspensions were prepared by trypsin treatment and cultured in melanocyte medium. Remaining keratinocytes were removed by differential trypsinization. 100μg/ml geneticin was used to eliminate the contaminating fibroblasts. At third passage, the cells were trypsinized, and then washed in phosphate-buffered saline and processed for transmission electron microscopy. Results： Under transmission electron microscope, the cultured cells showed round or oval shape, with single large nuclear and the karyotheca were double deck. There were obvious euchromosome within the nucleus, and sparse heterochromosome. There were various organelles in the cytoplasm, including plentiful melanosomes with nearly similar size, mitochondria, rough endoplasmic reticule （RER） and ribosome. The electron density granules in most of the melanosomes disposed along concentric circularities. Golgi apparatus in the cells was inconspicuous. Conclusion： The ultra structure of AMMC from human hair follicles is different from that of epidermal melanocytes, and these characteristics determine the functional immature of AMMC.

Direct Melanocytes Transplant from Normal Donor Area into Vitiliginous Recipient Area by Dermabrasion Technique

Background: Vitiligo is an autoimmune pigmentory disorder, that affects all age group that is treated by many medical treatments but some of them might need surgical therapy. Objective: To evaluate the dermabrasion technique in the treatment of vitiligo by direct transfer of melanocytes from the dermabraded normal donor area to the vitiliginous recipient area. Patients and Methods: This is a case interventional study was done in Department of Dermatology/Baghdad Teaching Hospital from February 2011-March 2012. Nine Patients with vitiligo were enrolled in this study with different clinical types of vitiligo including 5 segmental, 2 generalized and 2 localized. The donor and recipient areas were anesthetized at the same time with xylocain alone. Dermabrasion of recipient area was done first by manual abrader and left for few minutes until the oozing was stopped. Then the donor area was similarly dermabraded and the dermabraded tissue including the epidermis and superficial epidermis was immediately transferred into the recipient area and dressing was applied. Removal of the dressing was done after 10 - 14 days from the operative time. Follow up was done every 2 weeks in the first month then monthly for six months to record the result of implantation and repigmentation. Results: The re-pigmentation started one month after the operation as small macules and this increased gradually over time: the mean rate of re-pigmentation was 13% at 2 months, 27.8% at 4 months and 36.78% at 6 months. In addition, sun light exposure was applied to enhance re-pigmentation. The pigmentation was diffuse and not follicular in shape. Conclusion: Direct transfer of melanocytes from normal donor area into vitiliginous recipient area by dermabrasion technique was easy, rapid and non-costly and gave 36.78% mean rate of pigmentation at 6 months follow up and without complications.

Treatment of Gray Hair in Vitiligo Patients by Direct Melanocytes Transplant Using Needling Micrografting and Dermabrasion Techniques

Background: Melanocytes transplant for treatment of vitiligo is a common therapy using different surgical procedures. But there was no interest in repigmentation of grayness of hair in the treated vitiliginous area. Objective: To do melanocytes transplant from donor area into the recipient vitiliginous area with associated gray hair. Patient and Methods: This is a case interventional study was done in Department of Dermatology/Baghdad Teaching Hospital from February 2011-March 2012. Eleven patients were enrolled in this study, six males and five females with vitiligo in association of gray hair. Their ages ranged from 8 - 35 years with a mean ±SD of 20.90 ± 7.006. Melanocytes transplant in patients with vitiligo using needling micrografting technique for twelve patches and direct melanocytes transplant from normal donor area into vitiliginous recipient area by dermabrasion technique for eleven patches. Dressing was applied and patients were seen every two weeks for the first month and monthly for one year. Results: Repigmentation of the vitiliginous area was started after two weeks and was obvious at one month that progressed over time. The repigmentation of hair appeared usually after few months and was obvious after four months and the repigmentation of gray hair was quicker in patients with micrografting technique than those with dermabrasion technique. The mean rate of repigmentation was 18.3% at six months and 37.5% at twelve months in micrografting technique while the mean rate of repigmentation was 9.15% at six months and 18.55 at twelve months in dermabrasion technique. Conclusions: Direct transplant of melanocytes from normal donor area into recipient vitiliginous area with associated white hair is an effective procedure to induce repigmentation of gray hair.

Not Follicular but Dermal Melanocyte Precursors Are Histopathologically Retained in Vitiligo

Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF+/Fzd4+ cells in the hair follicle were significantly decreased in number in the lesions, Nestin+ and p75NGFR+ cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.

自体细胞移植治疗稳定期白癜风疗效的Meta分析

目的 系统评价培养与非培养自体黑色素细胞移植及联合其他方法治疗稳定期白癜风的疗效。方法检索PubMed、Embase、Web of Science、The Cochrane Library、中国期刊全文数据库(CNKI)、维普中文科技期刊全文数据库(VIP)、万方数据库,纳入研究为自体细胞移植治疗稳定期白癜风的临床研究。计数资料以合并后相对危险度(RR)值为效应指标,用Revman5.4软件对符合分析的研究进行Meta分析。结果 最终纳入文献14篇,Meta分析显示:自体培养黑色素细胞移植(CMT)与黑色素细胞+角质细胞、CMT与自体非培养混悬液移植(NCES)治疗稳定期白癜风疗效差异无统计学意义(P>0.05);CMT与CMT+光疗治疗稳定期白癜风疗效差异有统计学意义(P<0.01);NCES与NCES+其他成分、NCES与NCES+其他疗法、NCES与NCES+光疗治疗稳定期白癜风疗效差异无统计学意义(P>0.05);细胞移植与细胞移植+其他疗法、细胞移植与细胞移植+光疗、细胞移植与细胞移植+窄谱中波紫外线(NBUVB)治疗稳定期白癜风疗效差异有统计学意义(P<0.01)。结论 NCES和CMT移植治疗稳定期白癜风都有较好的疗效,与混悬液中所含成分无直接关系。黑色素细胞移植联合其他治疗方式治疗白癜风疗效要优于单一用黑色素细胞移植治疗白癜风。受纳入研究数量和质量限制,上述结论有待更多设计合理的随机对照临床研究证实。

1例大长径睑缘色素痣的超脉冲CO_(2)激光治疗体会

面积较大的睑色素缘痣并不常见,我们接收了1例长径较长的睑缘色素痣,用超脉冲CO_(2)激光进行治疗,操作简单,术后美容效果佳,是一种值得推荐的治疗方法,故对其进行报道。

哺乳动物毛色形成过程及黑色素细胞标志物研究进展

哺乳动物的毛色主要由黑色素细胞合成的黑色素决定。细胞着色过程包括黑色素细胞的发育、黑色素的合成与代谢及调节黑色素合成的信号通路等。黑色素细胞可被区分为多种类型,且这些类型可用多种黑色素细胞标志物来鉴定。毛色可以判断动物的身体状况和营养状况,并且毛色不同可能会对动物生产产生一定影响。文章综述了哺乳动物毛色形成的结构基础及其发育周期,描述了从神经嵴到驻留在几种组织中的成熟黑色素细胞的细胞色素化过程,总结了黑色素细胞的类型及各个类型黑色素细胞的标志物,讨论了动物毛色在动物生产中的应用,为解析哺乳动物毛色形成遗传机制提供帮助及为毛色影响的动物生产提供有效建议。

麝香草酚三甲氧基肉桂酸酯抑制黑色素生成、转移及AGEs合成的功效研究

基于皮肤细胞模型研究了麝香草酚三甲氧基肉桂酸酯的美白功效,采用CCK-8法和观察细胞状态检测麝香草酚三甲氧基肉桂酸酯对B16-F10细胞活率的影响;分别采用NaOH裂解法和多巴氧化法分析B16-F10细胞中黑色素含量和酪氨酸酶活性变化;采用细胞划痕法和Transwell小室法测定B16-F10细胞迁移能力变化;利用荧光分析法检测体外糖化实验中荧光性AGEs含量变化。结果表明麝香草酚三甲氧基肉桂酸酯质量浓度在10μg/mL及以下时对细胞活率没有明显影响,并且在10μg/mL时对黑色素合成、酪氨酸酶活性以及细胞迁移能力抑制率最高;200μg/mL时在体外对荧光性AGEs生成的抑制率达到97.75%。研究结果表明麝香草酚三甲氧基肉桂酸酯可以明显抑制黑色素的生成并抑制酪氨酸酶的活性,具有较好的美白功效;由于其同时具有较好的抗糖化能力,可作为潜在的抗衰老原料。

蓝光导致皮肤色素沉着的发生机制研究

蓝光是一种波长为400~500 nm的可见光,其对人体主要危害有损伤眼周及眼部结构、加速皮肤老化、抑制褪黑素分泌、造成皮肤色素沉着等。当前,关于蓝光导致皮肤色素沉着的研究较少,文章首次系统地整理了蓝光导致皮肤色素沉着的发生机制,其主要包含蓝光对视蛋白3、α-MSH-MC1R通路、黑皮素受体、细胞因子等产生影响最后导致黑素生成增加,引发皮肤色素沉着。为后续相关研究提供了思路与理论基础。

α-促黑素细胞激素在皮肤病治疗中的研究进展

α-促黑素细胞激素是一种神经内分泌激素,主要负责刺激毛发和皮肤中黑色素的产生。另外,它在控制食欲和能量平衡、性行为和缺血再灌注相关损伤等方面也发挥着重要作用。近年来,人们对开发α-促黑素细胞激素类似物有着很大的兴趣,并且已经初步用于治疗卟啉病、白癜风、家族性良性慢性天疱疮、多形性日光疹、日光性荨麻疹、寻常性痤疮等皮肤病。本文综述了α-促黑素细胞激素在皮肤病中的作用机制和治疗应用。

鲫腹膜分布、组织学及光照对其影响研究

腹膜在脊椎动物中普遍存在,由间皮细胞构成,通过结缔组织的支持作用形成的一层膜状组织,具有润滑、支持和保护等功能。鱼类有腹膜且分布有色素细胞,本研究选取常见经济鱼类鲫(Carassius auratus)为实验对象,采用组织学方法研究其腹膜分布及色素细胞形态特征,并探究光照条件对鲫腹膜色素细胞的影响。结果显示:(1)鲫腹膜呈黑色,腹腔腹壁内侧、心腹隔膜靠近腹腔一侧有明显分布,腹腔腹壁内侧黑色腹膜在腹腔上方延伸包裹性腺后相连覆于鳔下侧。(2)鲫腹膜黑色素细胞为黑色的树突状细胞。(3)鲫腹腔腹壁内侧腹膜的石蜡组织切片显示黑色素细胞连续分布形成黑色色素带,细胞核椭圆形、呈蓝紫色;扫描电镜下腹膜组织凹凸不平,由嵴组成多角形的网状结构;透射电镜下黑色素细胞有细胞核和黑素小体,黑素小体分为Ⅰ、Ⅱ、Ⅲ、Ⅳ四个时期。(4)不同光照影响鲫腹腔腹壁内侧腹膜黑色素细胞的形态,光照组黑色素细胞胞体变大、分支变粗,呈色变深;黑暗组黑色素细胞胞体变小、分支变细长。本研究为鱼类腹膜系统研究提供理论参考。

microRNA与皮肤衰老的研究进展

皮肤衰老是人体衰老最直观的表现,目前已发现皮肤衰老过程中伴着microRNA(miRNA)表达的改变。这表明miRNA可能参与了皮肤衰老过程的调控,可能有用于作为皮肤衰老的标志物和抗衰老治疗策略。本文旨在探讨miRNA如何通过影响皮肤角质形成细胞、成纤维细胞、免疫细胞及黑素细胞的增殖、分化、细胞稳定、蛋白通路、细胞周期等方面导致皮肤的衰老。

白驳丸及其拆方对白癜风小鼠CD8^(+)T细胞及黑素细胞的影响

目的探讨白驳丸及其拆方对白癜风小鼠CD8^(+)T细胞及黑素细胞的影响。方法正常C57BL/6小鼠作为空白组,同品系小鼠随机分为模型组、阳性药组、白驳丸及其拆方组。除空白组外,其余各组均构建内源性自身反应性CD8^(+)T细胞靶向皮肤黑素细胞的白癜风动物模型。造模成功后,分别予以托法替尼、白驳丸及其拆方水溶液灌胃,空白组及模型组等量纯水灌胃,各组小鼠均灌胃10周。采用小型摄影棚及数码相机拍摄小鼠尾部皮肤,Image J图像处理后观察皮损脱色情况;采用全组织包埋免疫荧光观察皮损CD8^(+)T细胞及黑素细胞数量及分布;采用流式细胞术观察皮损CD8^(+)T细胞及黑素细胞比例及功能。结果与空白组比较,模型组尾部皮损脱色面积增大,CD8^(+)T细胞浸润及黑素细胞缺失增多,CD3^(+)CD8^(+)T、CD8^(+)CD69^(+)T、CD8^(+)CXCR3^(+)T细胞比例增加,CD45^(-)CD117^(+)黑素细胞比例下降。与模型组比较,白驳丸及其拆方可不同程度改善白癜风小鼠尾部皮损脱色情况,减少CD8^(+)T细胞浸润及黑素细胞缺失,降低CD3^(+)CD8^(+)T、CD8^(+)CD69^(+)T、CD8^(+)CXCR3^(+)T细胞比例,增加CD45^(-)CD117^(+)黑素细胞比例;其中以白驳丸全方组效果最为显著,全方减养血活血通络药组效果最不明显。结论白驳丸及其拆方可不同程度地抑制CD8^(+)T细胞数量及功能,保护黑素细胞,改善白癜风小鼠尾部皮损脱色情况,其中养血活血通络药可能发挥核心作用。

先天性黑素细胞痣的发病机制及诊疗策略

先天性黑素细胞痣(Congenital melanocytic nevi,CMN)是一种常见的皮肤发育异常,可发生于人体任何有黑素细胞存在的部位。其发生与体细胞突变密切相关,受多种信号通路调控,临床表现多样。手术切除、扩张器应用仍是治疗CMN的主要方式,光电治疗是消除色素、清除卫星灶的有力手段。靶向、免疫治疗正成为治疗先天性黑色素巨痣的新方向。

黑白中药通过调节MC1R和RTKs的表达对黑色素代谢的影响研究

目的:探讨首乌、女贞子等七味黑色中药和白及、白芷等七味白色中药对豚鼠皮肤组织黑色素合成中黑皮质素1受体(Melanocortin 1 receptor,MC1R)、受体酪氨酸激酶(Receptor tyrosine kinase,RTKs)表达的影响。方法:采用水提法获得中药提取物,用灌胃的方法以14 d为周期等量灌胃豚鼠获得背部皮肤组织,采用免疫组化及免疫荧光法检测实验和对照组MC1R、RTKs蛋白的表达,用ImageJ软件统计分析结果,比较不同中药环境对豚鼠皮肤组织的黑色素合成的影响,分析MC1R、RTKs蛋白与黑素细胞代谢三者的变化关系。结果:对MC1R蛋白有抑制作用的白药有白芷、白茯苓、白蔹、白及、白僵蚕、白术,其中白芷、白僵蚕、白术的作用最为明显,对MC1R有明显抑制作用的黑药有乌梅、黑芝麻、丹参、鸡血藤,其中丹参的抑制作用最为明显。该结果显示上述10味中药对黑色素合成有抑制作用,其中白芷、白僵蚕、白术、丹参的抑制作用最为明显。其中对于RTKs蛋白有抑制作用的白药有白芷、白茯苓、白蔹、白及、白僵蚕,其中白茯苓、白蔹、白及的作用最为明显,具有明显作用的黑药有黑芝麻、丹参,其中丹参的作用最为明显。结论:药材颜色与药效之间有一定关系;黑白中药都对MC1R及RTKs蛋白有不同程度的抑制作用,色象中药可能通过调节α-黑素细胞剌激素/黑皮素1受体(Alphamelanocyte stimulating hormone/Melanocortin 1 receptor,α-MSH/M1CR)、干细胞生长因子/受体酪氨酸激酶(Stem cell growth factor/Receptor tyrosine kinase,SCF/RTKs)信号通路来影响黑素细胞代谢。