姜黄素对阿尔茨海默病小鼠海马InR和IGF1R表达的影响

目的观察姜黄素对阿尔茨海默病（Alzheimer＇sdisease,AD）模型APP／PS1双转基因小鼠胰岛素受体（insulinreceptor,InR）和胰岛素样生长因子1受体（insulin·likegrowthfactor1receptor,IGF1R）表达的影响。方法将3月龄的APP／PS1双转基因小鼠随机分为模型组、阳性罗格列酮对照组（每日10ms／kg）、姜黄素大（每日400mg／kg）、中（每日200mg／kg）、小剂量组（100mg／kg）,正常组为相同背景非转基因小鼠。灌胃3个月后,应用免疫组织化学和Westernblot方法进行检测。结果InR和IGF1R免疫组化染色,模型组小鼠大脑海马CA1区较正常对照组InR阳性细胞明显增加（P〈0．01）,姜黄素干预组有所恢复;而模型组小鼠大脑海马CA1区较正常对照组IGF1R阳性细胞明显减少（P〈0．01）,姜黄素干预组有所恢复。Western blot检测海马InR和IGF1R的蛋白表达结果与免疫组织化学检测结果一致。结论姜黄素可以使APP／PS1双转基因小鼠海马增加的InR和减少的IGF1R得以恢复,改善APP／PS1双转基因小鼠胰岛素信号转导。     

绵羊皮肤中GHR、IGF-1和IGF-1R基因表达的发育性变化及品种特点

采用相对定量反转录多聚酶链式反应 (RT-PCR)方法, 以18S rRNA作内标, 研究了罗米丽(Romilly Hillys)×中国美利奴(新疆军垦型)杂交一代优质细毛羊和哈萨克粗毛羊皮肤中生长激素受体(GHR)、胰岛素样生长因子1(IGF-1)和胰岛素样生长因子1受体(IGF-1R) mRNA发育性变化并进行了品种间比较。分别于30、60、90、135、180和255日龄称重、采毛样, 并于30、90、135和255日龄采皮样。结果表明: 粗毛羊和细毛羊体重、羊毛生长的发育模式没有明显的差异, 30~135日龄体重迅速增加, 135~255日龄增重十分缓慢; 30~135日龄羊毛日增长逐渐增加, 135~180日龄羊毛生长十分缓慢, 而180~255日龄又上升到较高水平。粗毛羊皮肤中GHR mRNA在30~90日龄显著增加 (P<0.05), 90日龄达到高峰, 此后显著下降(P<0.05); 细毛羊在135日龄时GHR mRNA极显著地升高(P<0.01), 此后又极显著地下降。粗毛羊皮肤中IGF-1、IGF-1R mRNA 30~90日龄上升, 90日龄之后极显著下降(P<0.01); 细毛羊皮肤中IGF-1、IGF-1R mRNA出生时较高, 然后逐渐下降。品种之间比较, 细毛羊GHR mRNA出现高峰晚于粗毛羊, 135日龄高峰时显著地高于粗毛羊; 粗毛羊IGF-1、IGF-1R mRNA在90日龄出现高峰, 并极显著或显著地高于细毛羊; 粗毛羊90日龄前GHR、IGF-1和IGF-1R mRNA高于细毛羊, 之后低于细毛羊。结果提示: 绵羊皮肤中GHR、IGF-1和IGF-1R基因表达有特定的发育模式, 并存在品种差异。     

二花脸和大白猪的脂肪组织中GH—R、IGF—1和IGF—IR基因表达的发育性变化

分别于出生当天、3、2 0、30、4 5、90、12 0、180日龄随机屠宰二花脸公、母猪各 4头 (30日龄仅有公猪 ) ,于 2 0、30、90、12 0、180日龄随机屠宰大白猪公猪 4头 ,采集背部皮下脂肪组织。用RT PCR方法 ,以 18SrRNA作内标 ,定量分析脂肪组织中生长激素受体 (GH R)、胰岛素样生长因子 1(IGF 1)及胰岛素样生长因子Ⅰ型受体 (IGF ⅠR)基因表达的发育性变化 ,并进行品种和性别间比较。结果表明 :脂肪组织中GH RmRNA的表达有明显的发育性变化及品种差异 ,二花脸母猪GH RmRNA水平出生时较低 ,4 5日龄达到高峰 ,之后维持稳定 ;二花脸公猪GH RmRNA水平在出生时较高 ,至 4 5日龄达到最高值 ,之后显著下降 ,但总体上没有性别差异 ;大白猪公猪GH RmRNA水平极显著低于二花脸公猪 (P <0 0 1)。脂肪组织中IGF 1mRNA的表达有明显的发育性变化及性别和品种差异 ,二花脸母猪显著低于公猪 (P <0 0 5 ) ,大白猪公猪极显著低于二花脸公猪 (P <0 0 1) ;脂肪组织中IGF ⅠRmRNA的表达有明显的发育性变化 ,但在总体上没有明显的性别和品种差异。结果提示 :猪脂肪组织中GH R、IGF 1和IGF ⅠR的基因表达有特定的发育模式 ,IGF 1基因表达的品种差异可能正是两品种猪脂肪沉积规律不同的主要原因之一。     

P75NTR在绒山羊毛囊生长周期中的表达

实验旨在研究绒山羊（Capra hircus）毛囊生长相关基因的表达规律,为绒山羊分子育种提供参考。本实验采用RTPCR、组织免疫荧光、Western blot等方法,研究神经营养素受体P75NTR在辽宁绒山羊皮肤组织中的表达和分布情况。结果表明：在毛囊生长周期的三个时期,均监测到P75NTR mRNA及蛋白的存在,P75NTR的荧光信号在退行期要强于其他两个时期,且在退行期毛囊外根鞘细胞中检测到P75NTR的高表达。以上结果表明,P75NTRmRNA及蛋白的表达与毛囊生长周期变化有一定的相关性,P75NTR受体在绒山羊的毛囊周期性变化中发挥着重要的功能。     

草鱼IGF—Ⅰ cDNA的克隆和在原核生物中的表达

根据亲缘关系较近的鲤鱼胰素样生长因子－Ⅰ（IGF－Ⅰ）cDNA设计一对引物,通过RT－PCR从草鱼（Ctenopharyngodon idellus）肝组织首次克隆了草鱼IGF－ⅠcDNA开放阅读框（ORF）片段,经序列分析表明克隆的草鱼IGF－ⅠcDNA为Ea－2亚型,ORF与鲤鱼有95％的同源性,与人有63％的同源性;草鱼IGF－Ⅰ蛋白与鲤鱼IGF－Ⅰ仅2个氨基酸残基不同,与人IGF－Ⅰ也仅有13个残基不同,将表达成熟草鱼IGF－Ⅰ(gcIGF-Ⅰ）蛋白的cDNA片段亚克隆至谷胱甘肽S－转移酶（GST）融合表达载体pGEX－4T－3,再将构建的重组表达载体pGEX-T-gcIGF-Ⅰ转入大肠杆菌BL21。在IPTG的诱导下,GST－gcIGF-Ⅰ融合蛋白高效表达。兔抗鲑鱼IGF－Ⅰ抗血清进行了Western Blot检测显示重组草鱼IGF－Ⅰ蛋白具有免疫活性。     

IGF-1及IGF-1R在胃癌中的表达及意义

目的探讨胰岛素样生长因子1(insulin-like growth factor-1,IGF-1)及胰岛素样生长因子1受体(insulin-like growth factor-1receptor,IGF-1R)在胃癌及癌旁胃黏膜组织中的表达及意义。方法采用免疫组化MaxVision两步法检测80例胃癌和50例癌旁胃黏膜组织中IGF-1及IGF-1R蛋白的表达,并分析两者与胃癌患者临床病理指标间的关系及其相关性。结果 IGF-1及IGF-1R蛋白在胃癌组织中表达阳性率分别为71.25%和75.00%,在癌旁胃黏膜组织中表达阳性率分别为30.00%和24.00%,差异有统计学意义(Z=-4.942,P0.001;Z=-5.688,P0.001)。IGF-1及IGF-1R蛋白的表达与胃癌的组织分化程度、有无淋巴结转移、浸润深度及临床分期相关(Z=-2.067、-2.837,P0.05;Z=-4.117、-3.579,P0.05;Z=-2.885、-2.836,P0.05;Z=-3.286、-3.313,P0.05)。相关性分析显示两者表达呈正相关。结论 IGF-1和IGF-1R蛋白在胃癌组织中呈高表达,两者可能在胃癌的发生、发展过程中具有协同及相互调节的作用。IGF-1和IGF-1R蛋白可能成为胃癌早期诊断、评估胃癌患者预后的重要指标。     

结肠癌细胞株和组织中EGFR、p-EGFR和p-IGFR-1β的表达及意义

目的：研究EGFR、p-EGFR和p-IGFR-1β在结肠癌细胞株的表达及其与吉非替尼敏感性的关系,以及在肿瘤组织中的表达状况、相关性及其与临床病理参数的关系。方法：以western blot检测EGFR、p-EGFR和p-IGFR-1β在结肠癌细胞株和组织中的表达,以Quantity One软件测量各蛋白条带的灰度值。结果：EGFR、p-EGFR在Lovo细胞中表达量最高（P〈0.05）,EGFR在SW620细胞中的表达最低（P〈0.05）,在HCT116、HT29、LS174T和SW480细胞中的表达差异不显著。p-IGFR-1β在Lovo、HT29和SW480细胞中表达较弱,且在Lovo细胞中表达更弱,但在HCT116、LS174T和SW620细胞中的表达均较强（P〈0.05）。结肠癌组织中EGFR表达率为55.6%（10/18）,癌旁正常组织为37.5%（3/18）,肿瘤组织中有表达增高的趋势;p-EGFR在结肠癌组织表达率为33.3%（6/18）,较正常组织的5.6%（1/18）明显增高（P〈0.05）;p-IGFR-1β在结肠癌组织表达率为44.4%（8/18）,较正常组织的11．1％（2／18）明显增高（P〈0．05）。EGFR、P-EGFR和P-IGFR-1β相互之间的表达无明显相关性;EGFR、P-EGFR表达与各临床病理参数无明显相关;P．IGFR-1β在淋巴结转移患者中的表达显著增高（P〈0．05）,且在分期晚的患者中也可观察到这种趋势。结论：结合我们以往的研究结果,P．EGFR表达高伴p-IGFR-1β表达低提示结肠癌细胞对吉非替尼的敏感性好。P-EGFR和P—IGFR-1β在结肠癌组织中的表达较正常组织明显增高,且p-IGFR．1B表达高可能预示结肠癌患者有较高的转移风险。     

野生型小鼠皮肤cyclinA1 mRNA的表达及其意义

目的从RNA水平探讨cyclinA1在野生型小鼠皮肤中的表达及意义。方法选取30只大于6个月的野生型小鼠,用原位杂交方法定位检测cyclinA1 mRNA在头颈部皮肤中的表达,同时以不加探针皮肤标本作为阴性对照,另取雄性小鼠睾丸组织作为阳性对照。结果分别有25只野生型小鼠在皮脂腺部位及12只在表皮全层有cyclinA1 mRNA表达。其中,皮脂腺部位强阳性及阳性表达分别占50.0%和33.3%,阳性率为83.3%;表皮全层强阳性及阳性表达分别占13.3%和26.7%,阳性率为40.0%。皮脂腺阳性率显著高于表皮(P0.05)。结论CyclinA1 mRNA在野生型小鼠头颈部皮肤的皮脂腺部位及表皮全层的表达均有较高的阳性率,尤其皮脂腺表达的阳性率更高。     

猪脂肪组织中IGF2和IGFBP3基因表达的发育性变化及其品种差异

采用荧光定量PCR技术分析长白猪和太湖猪背部皮下脂肪组织中胰岛素样生长因子2和胰岛素样生长因子结合蛋白3基因在30、60、90、120和150日龄时表达水平的发育性变化。结果表明: (1)品种内日龄间比较, 长白猪IGF2 mRNA 在30日龄时的表达量极显著高于其他日龄(P<0.01), 之后逐渐下降, 至120日龄降到最低, 150日龄时又明显上升; 太湖猪IGF2 mRNA在30~60日龄的表达量较高, 90日龄降至最低, 120日龄迅速回升, 之后又有所下降。两品种IGFBP3 mRNA表达的发育性变化模式基本相同, 30日龄时表达量最高, 60日龄显著下降(P<0.05), 之后趋于平缓但略有波动。(2)品种间同日龄比较, 120日龄时太湖猪IGF2 mRNA的表达量极显著高于长白猪(P<0.01), 150日龄时太湖猪IGFBP3的表达量极显著低于长白猪(P<0.01), 其余日龄间两品种差异均不显著(P>0.05)。研究结果提示: 猪脂肪组织IGF2和IGFBP3基因表达存在明显的发育性变化和品种差异; IGF2基因表达水平的降低可能与脂肪细胞的增殖有关。     

IGF-1对高糖诱导的小鼠早期胚胎凋亡的抑制作用

目的探讨胰岛素样生长因子1(IGF-1)对体外培养小鼠囊胚细胞凋亡的抑制作用。方法获取妊娠3.5d小鼠囊胚,分别移入3个培养皿中,分别为A、B、C三组:A组(基础培养液);B组(基础培养液+30mmol/L的葡萄糖溶液);C组(基础培养液+30mmol/L的葡萄糖溶液+100ng/ml的人重组IGF-1)。连续培养72h后,采用免疫组化S-P法检测各组囊胚细胞中Bax和Fas的表达,利用计算机图像分析技术测量各组囊胚细胞中Bax和Fas蛋白表达的平均光密度和平均阳性面积。结果B组囊胚细胞中Bax和Fas的表达明显高于A组和C组(P0.05)结论IGF-1对高糖诱导的小鼠着床前早期胚胎凋亡起了抑制作用。     

小鼠毛囊不同生长周期中MITF下游色素相关基因的定位表达及相关性分析

小眼畸形转录因子（MITF）不仅是黑色素细胞发育、增殖和存活的必要调节因子,而且对调节相关酶和黑素体蛋白表达来确保黑色素产生具有至关重要的作用。MITF下游色素相关基因在小鼠毛囊生长周期中的表达及相关性仍有待研究。HE染色结果表明不同毛囊时期的小鼠毛囊呈现典型的组织形态学结构;免疫组织化学显示,MITF、GPNMB、OA1、TYR、TYRP2在不同毛囊生长周期中的毛基质及内外毛根鞘均有不同程度的阳性表达。黑色素测定结果表明,在毛囊生长初期和中期,碱性可溶性总黑色素（ASM）、真黑素（EM）以及褐黑素（PM）相对含量高于毛囊生长末期。蛋白免疫印迹结果表明,MITF、GPNMB、OA1、TYR、TYRP2在毛囊生长初期和中期蛋白质相对水平明显高于毛囊生长末期。实时荧光定量PCR结果表明, MITF、GPNMB、OA1、TYR、TYRP2、PMEL在毛囊生长初期和中期,mRNA相对表达量显著高于毛囊生长末期。在不同毛囊生长周期小鼠皮肤的MITF下游色素相关基因表达存在显著差异,表明上述因子在维持黑色素细胞色素生成是不可或缺的因素。     

Differential Expression of Proteins Associated with the Hair Follicle Cycle - Proteomics and Bioinformatics Analyses

Hair follicle cycling can be divided into the following three stages: anagen, catagen, and telogen. The molecular signals that orchestrate the follicular transition between phases are still unknown. To better understand the detailed protein networks controlling this process, proteomics and bioinformatics analyses were performed to construct comparative protein profiles of mouse skin at specific time points (0, 8, and 20 days). Ninety-five differentially expressed protein spots were identified by MALDI-TOF/TOF as 44 proteins, which were found to change during hair follicle cycle transition. Proteomics analysis revealed that these changes in protein expression are involved in Ca²⁺-regulated biological processes, migration, and regulation of signal transduction, among other processes. Subsequently, three proteins were selected to validate the reliability of expression patterns using western blotting. Cluster analysis revealed three expression patterns, and each pattern correlated with specific cell processes that occur during the hair cycle. Furthermore, bioinformatics analysis indicated that the differentially expressed proteins impacted multiple biological networks, after which detailed functional analyses were performed. Taken together, the above data may provide insight into the three stages of mouse hair follicle morphogenesis and provide a solid basis for potential therapeutic molecular targets for this hair disease.     

Mouse Hair Cycle Expression Dynamics Modeled as Coupled Mesenchymal and Epithelial Oscillators

The hair cycle is a dynamic process where follicles repeatedly move through phases of growth, retraction, and relative quiescence. This process is an example of temporal and spatial biological complexity. Understanding of the hair cycle and its regulation would shed light on many other complex systems relevant to biological and medical research. Currently, a systematic characterization of gene expression and summarization within the context of a mathematical model is not yet available. Given the cyclic nature of the hair cycle, we felt it was important to consider a subset of genes with periodic expression. To this end, we combined several mathematical approaches with high-throughput, whole mouse skin, mRNA expression data to characterize aspects of the dynamics and the possible cell populations corresponding to potentially periodic patterns. In particular two gene clusters, demonstrating properties of out-of-phase synchronized expression, were identified. A mean field, phase coupled oscillator model was shown to quantitatively recapitulate the synchronization observed in the data. Furthermore, we found only one configuration of positive-negative coupling to be dynamically stable, which provided insight on general features of the regulation. Subsequent bifurcation analysis was able to identify and describe alternate states based on perturbation of system parameters. A 2-population mixture model and cell type enrichment was used to associate the two gene clusters to features of background mesenchymal populations and rapidly expanding follicular epithelial cells. Distinct timing and localization of expression was also shown by RNA and protein imaging for representative genes. Taken together, the evidence suggests that synchronization between expanding epithelial and background mesenchymal cells may be maintained, in part, by inhibitory regulation, and potential mediators of this regulation were identified. Furthermore, the model suggests that impairing this negative regulation will drive a bifurcation which may represent transition into a pathological state such as hair miniaturization.     

Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids

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Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle

The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr), which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes.     

Wnt3a在毛囊及黑素细胞谱系中的表达

目的:探讨毛囊周期中,Wnt3a在毛囊及黑素细胞中的表达变化。方法:以DCT-LacZ转基因小鼠为动物模型,通过X-gal染色技术观察黑素细胞谱系在小鼠皮肤中的分布情况;采用X-gal染色结合免疫组化方法检测Wnt3a在毛囊及黑素细胞谱系中的表达情况;采用RT-PCR方法对小鼠皮肤全层Wnt3a和TYR的mRNA表达进行半定量分析。结果:在生长期毛囊中,Wnt3a蛋白在表皮、毛囊外根鞘Bulge区、内根鞘以及毛球部均有表达,在黑素干细胞与黑素细胞也观察到Wnt3a;在退化期,Wnt3a的表达逐渐减弱,仅在外根鞘有较弱的表达,但黑素干细胞中没有观察到Wnt3a;在静止期,几乎检测不到Wnt3a的表达;TYR mRNA与Wnt3a mRNA在毛囊周期中的表达模式一致,在生长期最强,退化期减弱,静止期最弱。结论:Wnt3a可能对黑素细胞谱系分化起到促进作用。     

The Patchwork Mouse Phenotype: Implication for Melanocyte Replacement in the Hair Follicle

Mice homozygous for the recessive patchwork (pwk) mutation are characterized by a variegated pigment pattern with a mixture of unpigmented and normally pigmented hairs. The pigmented hair bulbs contain functional melanocytes. By contrast, the unpigmented hair bulbs contain no melanocytes. This lack results from the death of melanoblasts in the hair follicle at the end of embryogenesis. Here, we report that melanoblasts and melanocytes are found in the epidermis of pwk/pwk mice. Furthermore, these epidermal pigment cells are able to colonize new hair follicles after skin wounding. Despite the presence of epidermal pigment cells with a colonization potential, a follicle that had produced an unpigmented hair produces a new unpigmented hair during the successive hair growth cycles. This hair color continuity is also true for the pigmented hair follicles. Thus, in normal conditions, the hair acts as an independent functional unit as regards its pigment cells population.     

Impaired IGF1R signaling in cells expressing longevity-associated human IGF1R alleles

Dampening of insulin/insulin-like growth factor-1 (IGF1) signaling results in the extension of lifespan in invertebrate as well as murine models. The impact of this evolutionarily conserved pathway on the modulation of human lifespan remains unclear. We previously identified two IGF1R mutations (Ala-37-Thr and Arg-407-His) that are enriched in Ashkenazi Jewish centenarians as compared to younger controls and are associated with the reduced activity of the IGF1 receptor as measured in immortalized lymphocytes. To determine whether these human longevity-associated IGF1R mutations affect IGF1 signaling, we engineered mouse embryonic fibroblasts (MEFs) expressing the different human IGF1R variants in a mouse Igf1r null background. The results indicate that MEFs expressing the human longevity-associated IGF1R mutations attenuated IGF1 signaling, as demonstrated by significant reduction in phosphorylation of both IGF1R and AKT after IGF1 treatment, in comparison with MEFs expressing the wild-type IGF1R. The impaired IGF1 signaling caused by the IGF1R mutations resulted in the reduced induction of the major IGF1-activated genes in MEFs, including EGR1, mCSF, IL3Rα, and TDAG51. Furthermore, the IGF1R mutations caused a delay in cell cycle progression after IGF1 treatment, indicating a dysfunctional physiological response to a cell proliferation signal. These results demonstrate that the human longevity-associated IGF1R variants are reduced-function mutations, implying that dampening of IGF1 signaling may be a longevity mechanism in humans.     

Decoy Oligonucleotide Rescues IGF1R Expression from MicroRNA-223 Suppression

A mature miRNA generally suppresses hundreds of mRNA targets. To evaluate the selective effect of synthetic oligonucleotide decoys on hsa-miR-223 activity, reporters containing 3’ untranslated regions (UTR) of IGF1R, FOXO1, POLR3G, FOXO3, CDC27, FBXW7 and PAXIP1 mRNAs were constructed for the luciferase assay. The oligonucleotide decoys were designed and synthesized according to mature miR-223 sequence and its target mRNA sequence. Quantitative RT-PCR & western analysis were used to measure miR-223-targeted mRNA expression, Interestingly, apart from the antisense oligonucleotide, decoy nucleotides which were complementary to the 5’, central or 3’ region of mature miR-223 suppressed miR-223 targeting the 3’UTR of IGF1R, FOXO1, FOXO3, CDC27, POLR3G, and FBXW7 mRNAs and rescued the expression of these genes to varying degrees from miR-223 suppression at both mRNA and protein levels. All decoys had no effect on PAXIP1 which was not targeted by miR-223. The decoy 1 that was based on the sequence of IGF1R 3’UTR rescued the expression of IGF1R more significantly than other decoy nucleotides except the antisense decoy 4. Decoy 1 also rescued the expression of FOXO3 and POLR3G of which their 3’UTRs have similar binding sites for miR-223 with IGF1R 3’UTR. However decoy 1 failed to recover Sp1, CDC27 and FBXW7 expression. These data support that the sequence-specific decoy oligonucleotides might represent exogenous competing RNA which selectively inhibits microRNA targeting.     

敲除非受体酪氨酸激酶c-Abl促进小鼠毛发循环和再生

c-Abl作为非受体酪氨酸激酶家族的成员,参与调节多个组织器官的发育过程,如神经、血管及骨骼等。c-Abl的异常激活也往往导致神经退行性疾病或肿瘤的发生。到目前为止,c-Abl在皮肤和毛发器官中的研究非常少。本研究首先分析了c-Abl基因在皮肤和毛囊中的动态表达情况,发现在毛囊上皮有丰富的表达,然后利用表皮特异性工具小鼠K14-Cre将c-Abl基因在表皮敲除,发现毛囊由静息期向生长期的转换略有加快。小鼠脱毛实验发现,当所有毛囊都从头开始再生时,突变鼠的毛囊起始比对照小鼠更快。这些结果均表明,在表皮敲除c-Abl基因能够导致毛发循环和毛囊再生的加快。进一步的研究发现,以上表型可能是c-Abl通过调节BMP信号通路造成的。我们的工作首次研究了c-Abl基因在皮肤毛囊中的动态表达,揭示了c-Abl通过BMP信号通路调节毛囊再生的机制。