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The Emerging Therapeutic Targets for Scar Management: Genetic and Epigenetic Landscapes 疤痕管理的新兴治疗靶点:遗传和表观遗传景观
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-06-13 DOI: 10.1159/000524990
Sara Amjadian, S. Moradi, P. Mohammadi
Background: Wound healing is a complex process including hemostasis, inflammation, proliferation, and remodeling during which an orchestrated array of biological and molecular events occurs to promote skin regeneration. Abnormalities in each step of the wound healing process lead to reparative rather than regenerative responses, thereby driving the formation of cutaneous scar. Patients suffering from scars represent serious health problems such as contractures, functional and esthetic concerns as well as painful, thick, and itchy complications, which generally decrease the quality of life and impose high medical costs. Therefore, therapies reducing cutaneous scarring are necessary to improve patients’ rehabilitation. Summary: Current approaches to remove scars, including surgical and nonsurgical methods, are not efficient enough, which is in principle due to our limited knowledge about underlying mechanisms of pathological as well as the physiological wound healing process. Thus, therapeutic interventions focused on basic science including genetic and epigenetic knowledge are recently taken into consideration as promising approaches for scar management since they have the potential to provide targeted therapies and improve the conventional treatments as well as present opportunities for combination therapy. In this review, we highlight the recent advances in skin regenerative medicine through genetic and epigenetic approaches to achieve novel insights for the development of safe, efficient, and reproducible therapies and discuss promising approaches for scar management. Key Message: Genetic and epigenetic regulatory switches are promising targets for scar management, provided the associated challenges are to be addressed.
背景:伤口愈合是一个复杂的过程,包括止血、炎症、增殖和重塑,在此过程中,会发生一系列生物和分子事件来促进皮肤再生。伤口愈合过程中每一步的异常都会导致修复反应,而不是再生反应,从而导致皮肤疤痕的形成。患有疤痕的患者代表着严重的健康问题,如挛缩、功能和美观问题,以及疼痛、粘稠和瘙痒的并发症,这些并发症通常会降低生活质量并带来高昂的医疗成本。因此,减少皮肤疤痕的治疗对于改善患者的康复是必要的。总结:目前去除疤痕的方法,包括手术和非手术方法,不够有效,原则上是由于我们对病理和生理伤口愈合过程的潜在机制了解有限。因此,专注于基础科学(包括遗传和表观遗传学知识)的治疗干预措施最近被认为是疤痕管理的有前途的方法,因为它们有潜力提供靶向治疗,改善传统治疗,并为联合治疗提供机会。在这篇综述中,我们强调了皮肤再生医学的最新进展,通过遗传和表观遗传学方法,为开发安全、高效和可重复的疗法获得了新的见解,并讨论了有前景的疤痕管理方法。关键信息:遗传和表观遗传学调控开关是疤痕管理的有希望的靶点,前提是相关的挑战有待解决。
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引用次数: 5
Dexamethasone, a Synthetic Glucocorticoid, Induces the Activity of Androgen Receptor in Human Dermal Papilla Cells 合成糖皮质激素地塞米松诱导人真皮乳头细胞雄激素受体活性的研究
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-05-13 DOI: 10.1159/000525067
M. Kwack, O. Ben Hamida, M. Kim, Jung Chul Kim, Y. Sung
Psychosocial stress stimulates the secretion of glucocorticoids (GCs), which are stress-related neurohormones. GCs are secreted from hair follicles and promote hair follicle regression by inducing cellular apoptosis. Moreover, the androgen receptor (AR) is abundant in the balding scalp, and androgens suppress hair growth by binding to AR in androgenetic alopecia. First, by using immunofluorescence, we investigated whether the treatment of dermal papilla (DP) cells with dexamethasone (DEX), a synthetic GC, causes the translocation of the glucocorticoid receptor (GR) into the nucleus. DEX treatment causes the translocation of the GR into the nucleus. Next, we investigated whether stress-induced GCs affect the AR, a key factor in male pattern baldness. In this study, we first assessed that DEX increases the expression of AR mRNA in non-balding DP cells, which rarely express AR without androgen. RU486, a GR antagonist, attenuated DEX-inducible AR mRNA expression and AR activation in human non-balding DP cells. In addition, AR translocated into the nucleus after DEX treatment. Furthermore, we indeed showed that the expression of AR was induced in the nucleus by DEX in DP cells of human and mouse hair follicles. Our results first suggest that stress-associated hair loss may be due to increased AR expression and activity induced by DEX. These results demonstrate that hair loss occurs in non-balding scalps with low AR expression.
心理社会压力刺激糖皮质激素(GC)的分泌,这是一种与压力相关的神经激素。GC从毛囊分泌,并通过诱导细胞凋亡促进毛囊退化。此外,雄激素受体(AR)在脱发的头皮中含量丰富,雄激素通过与AR结合来抑制雄激素性脱发的头发生长。首先,通过使用免疫荧光,我们研究了用地塞米松(DEX)(一种合成的GC)处理毛乳头(DP)细胞是否会导致糖皮质激素受体(GR)易位到细胞核中。DEX治疗导致GR易位进入细胞核。接下来,我们研究了应激诱导的GC是否影响AR,AR是男性型秃发的关键因素。在这项研究中,我们首先评估了DEX增加了非秃头DP细胞中AR mRNA的表达,而在没有雄激素的情况下,这些细胞很少表达AR。RU486是一种GR拮抗剂,可减弱DEX诱导的人非脱发DP细胞中AR mRNA的表达和AR的激活。此外,在DEX处理后,AR转移到细胞核中。此外,我们确实表明,在人类和小鼠毛囊的DP细胞中,DEX在细胞核中诱导了AR的表达。我们的研究结果首先表明,应激相关的脱发可能是由于DEX诱导的AR表达和活性增加。这些结果表明,脱发发生在AR表达低的非脱发头皮中。
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引用次数: 2
Front & Back Matter 正面和背面
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-05-01 DOI: 10.1159/000524836
J. Fluhr, M. Lane
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引用次数: 0
A Composite of Hepatocyte Growth Factor- and 5α-Dihydrotestosterone-Gelatin Microspheres with Adipose-Derived Stem Cells Enhances Wound Healing 肝细胞生长因子-和5α-二氢睾酮明胶微球与脂肪来源干细胞的复合物增强伤口愈合
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-04-19 DOI: 10.1159/000524188
K. Tao, X. Bai, P. Ji, Yue Zhang, Tao Cao, F. Han, Zhi Zhang, Hao Guan, D. Hu
Introduction: Reconstructing sebaceous glands is one goal of functionally healing patients who have suffered severe burns, instead of the simple pursuit of wound closure. Effective regeneration of skin appendages remains a challenge in skin wound management and research. Objective: The aim of this study was to evaluate the differentiation of adipose-derived stem cells (ADSCs) into sebaceous glands and clarified the involvement of hepatocyte growth factor (HGF) and 5α-dihydrotestosterone (5α-DHT) in this process. Methods: This study used HGF- and 5α-DHT-gelatin microspheres to treat human ADSCs and investigated the reconstruction of sebaceous glands. HGF- and 5α-DHT-gelatin microspheres were constructed using microcapsule slow-release technology. A mice full-thickness skin-wound model was established to evaluate wound healing, and hematoxylin-eosin staining was utilized to determine the skin structure. Results: In vitro analyses found that HGF- and 5α-DHT-gelatin microspheres promoted migration of and tube formation by ADSCs. Furthermore, AKT/ERK signaling, which is related to sebocyte and sweat gland epithelial-cell growth, was activated after HGF and 5α-DHT treatment. An in vivo wound healing model demonstrated that ADSCs primed with amnion-loaded HGF- and 5α-DHT-gelatin microspheres promoted wound healing and increased sebaceous gland formation compared to the control group. Conclusions: This study confirms the efficacy of ADSCs treated with amnion and HGF- and 5α-DHT-gelatin microspheres in accelerating wound healing and effectively restoring sebaceous glands. This engineered tissue provides insight into and a novel therapeutic material for burns and full-thickness skin wounds.
简介:重建皮脂腺是功能性治愈严重烧伤患者的目标之一,而不是简单地追求伤口闭合。皮肤附属物的有效再生仍然是皮肤伤口管理和研究中的一个挑战。目的:本研究旨在评估脂肪干细胞(ADSCs)向皮脂腺的分化,并阐明肝细胞生长因子(HGF)和5α-二氢睾酮(5α-DHT)在这一过程中的作用。方法:采用HGF-和5α-DHT明胶微球治疗人ADSCs,并研究其对皮脂腺的重建作用。采用微胶囊缓释技术构建了HGF-和5α-DHT明胶微球。建立小鼠全层皮肤伤口模型以评估伤口愈合,并使用苏木精-伊红染色来确定皮肤结构。结果:体外分析发现,HGF-和5α-DHT明胶微球促进了ADSCs的迁移和成管。此外,与皮脂细胞和汗腺上皮细胞生长有关的AKT/ERK信号传导在HGF和5α-DHT处理后被激活。体内伤口愈合模型表明,与对照组相比,用羊膜负载的HGF-和5α-DHT明胶微球引发的ADSCs促进了伤口愈合并增加了皮脂腺的形成。结论:本研究证实了羊膜和HGF-和5α-DHT明胶微球治疗ADSCs在加速伤口愈合和有效修复皮脂腺方面的疗效。这种工程组织为烧伤和全层皮肤伤口提供了深入了解和新型治疗材料。
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引用次数: 1
Induction of Radiodermatitis in Nude Mouse Model Using Gamma Irradiator IBL 637 γ辐照剂ibl637诱导裸鼠放射性皮炎
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-04-13 DOI: 10.1159/000524596
T. Bernhardt, S. Kriesen, K. Manda, Christin Schlie, R. Panzer, G. Hildebrandt, B. Vollmar, S. Emmert, L. Boeckmann
Introduction: Acute radiodermatitis is a common, though severe, side effect of radiotherapy against cancer that may lead to an interruption or even abortion of the radiotherapy. Mouse models provide an excellent tool to study pathomechanisms of a radiation-induced dermatitis as well as to test and develop novel innovative treatment strategies. Objective: The aim of this study was to provide an overview of different mouse models and irradiation devices that have been used so far and to describe the process of the induction of a radiation dermatitis in an immune proficient nude mouse model (SKH1-Hrhr) using a IBL 637 cesium-137γ-ray machine. Methods: This process includes the construction of a radiation shielding chamber, restricting the radiation to the right hind leg of the mouse, a dosimetry, and a dose finding study to identify the appropriate irradiation dose to induce a moderate radiation dermatitis. Results: A radiation shielding chamber was successfully constructed allowing selective irradiation of the right hind leg. A moderate radiodermatitis is induced with irradiation doses in the range of 60–70 Gy under the here described conditions. Symptoms peak about 8 days after irradiation and decrease relatively quickly thereafter. Histological analyses confirmed typical signs of inflammation. Conclusion: This study describes for the first time a protocol to induce a moderate radiodermatitis in the nude mouse model SKH1-Hrhr using a IBL 637 gamma irradiator. This protocol will allow researchers to study novel treatment strategies to alleviate the burden of a radiodermatitis as a side effect of cancer treatment.
简介:急性放射性皮炎是放疗治疗癌症时常见但严重的副作用,可能导致放疗中断甚至流产。小鼠模型为研究辐射性皮炎的病理机制以及测试和开发新的创新治疗策略提供了一个很好的工具。目的:本研究的目的是概述迄今为止使用的不同小鼠模型和照射装置,并描述使用IBL 637铯-137γ射线机诱导免疫熟练裸鼠模型(SKH1-Hrhr)辐射皮炎的过程。方法:建立辐射屏蔽室,将辐射限制在小鼠右后肢,进行剂量测定和剂量测定研究,以确定诱导中度放射性皮炎的适当辐照剂量。结果:成功构建了右后腿选择性照射的辐射屏蔽室。在这里描述的条件下,用60-70戈瑞范围内的辐照剂量诱发中度放射性皮炎。照射后约8天症状达到高峰,此后症状减轻较快。组织学分析证实了典型的炎症症状。结论:本研究首次描述了一种使用IBL 637 γ辐照剂诱导裸鼠模型SKH1-Hrhr中度放射性皮炎的方案。该方案将使研究人员能够研究新的治疗策略,以减轻放射性皮炎作为癌症治疗副作用的负担。
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引用次数: 1
Correlation of Body Mass Index with Epidermal Biophysical Properties Varies with Gender in Chinese 中国人体重指数与表皮生物物理特性的相关性因性别而异
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-04-04 DOI: 10.1159/000524295
L. Ye, Q. Lai, S. Wen, Xiaohua Wang, Bin Yang, M. Man
Background: Epidermal function is associated with diabetes and renal disease. Whether obesity can reflect the changes in epidermal function is not clear yet. Objective: We assessed here the correlation of epidermal functions with body mass index (BMI) in a large Chinese cohort. Methods and Subjects: A total of 1,405 Chinese aged 21–98 years old were enrolled in this study. Epidermal functions, including transepidermal water loss (TEWL), stratum corneum hydration, and skin surface pH, were measured on the flexor forearm and the shin. Subjects’ height and body weight were also measured. Results: Age positively correlated with both TEWL and skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin of females. Similarly, age positively correlated with skin surface pH, while negatively correlating with stratum corneum hydration on both the forearm and the shin of males. In females, BMI positively correlated with skin surface pH, while it negatively correlated with stratum corneum hydration on both the forearm and the shin. However, BMI correlated neither with skin surface pH on both the forearm and the shin nor with stratum corneum hydration on the shin of males. Conclusion: These results demonstrate that correlations of BMI with age and epidermal functions vary with gender.
背景:表皮功能与糖尿病和肾脏疾病有关。肥胖是否能反映表皮功能的变化尚不清楚。目的:我们在一个大型中国队列中评估了表皮功能与体重指数(BMI)的相关性。方法和受试者:本研究共招募了1405名年龄在21-98岁之间的中国人。测量前臂屈肌和胫骨的表皮功能,包括经表皮失水(TEWL)、角质层水合作用和皮肤表面pH值。还测量了受试者的身高和体重。结果:女性的年龄与TEWL和皮肤表面pH呈正相关,而与前臂和胫骨的角质层水合作用呈负相关。同样,年龄与男性前臂和胫骨的皮肤表面pH呈正相关,而与角质层水合作用呈负相关。在女性中,BMI与皮肤表面pH呈正相关,而与前臂和胫骨的角质层水合作用呈负相关。然而,BMI既与前臂和胫骨的皮肤表面pH值无关,也与男性胫骨的角质层水合作用无关。结论:这些结果表明,BMI与年龄和表皮功能的相关性因性别而异。
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引用次数: 8
LncRNA XIST Engages in Psoriasis via Sponging miR-338-5p to Regulate Keratinocyte Proliferation and Inflammation LncRNA-XIST通过启动miR-338-5p调节角质形成细胞增殖和炎症参与银屑病
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-03-01 DOI: 10.1159/000523781
Yitao Wang, Feifei Jiang, Fang Chen, Dapeng Zhang, Jian Wang
Introduction: Psoriasis is an immune-mediated polygenic inflammatory skin disease in which keratinocyte proliferation is an important mechanism. The study investigated the role and regulatory relationship between lncRNA XIST and miR-338-5p in psoriatic patients and cell models. Methods: Serum samples were collected from 55 psoriasis patients. HaCaT was recruited for the cell experiments, and induced by M5 cytokines to mimic psoriasis in vitro. XIST and miR-338-5p levels were detected via qRT-PCR. Cell viability under different treatments was evaluated using CCK-8. ELISA was applied to measure the concentration of inflammatory cytokines. The regulatory relationship was confirmed using luciferase reporter gene assay. Results: Serum XIST was elevated in patients with psoriasis and can distinguish the psoriasis patients from healthy controls according to the receiver operating characteristic curve. A high level of XIST was positively correlated with the PASI score and serum tumor necrosis factor-alpha (TNF-α), interleukin-17A [IL-17A], and IL-22 concentrations in psoriasis patients. XIST silencing suppressed M5-induced keratinocyte proliferation and restrained the discharge of inflammatory cytokines (TNF-α, IL-17A, IL-22) and chemokines (CXCL1, CXCL8, CCL20). XIST can sponge miR-338-5p, and miR-338-5p downregulation abolished the inhibitory effect of XIST silencing on cell proliferation and inflammation. miR-338-5p was highly expressed in the clinical serum samples from psoriasis patients. The target relationship between miR-338-5p and IL-6 was proved. Conclusion: LncRNA XIST is highly expressed in the serum of patients with psoriasis, and was positively correlated with disease severity and inflammation. XIST may regulate keratinocyte proliferation and inflammation via regulating miR-338-5p/IL-6 axis.
银屑病是一种免疫介导的多基因炎症性皮肤病,角质细胞增殖是其重要机制。本研究探讨lncRNA XIST与miR-338-5p在银屑病患者及细胞模型中的作用及调控关系。方法:采集55例银屑病患者血清标本。我们招募HaCaT进行细胞实验,并通过M5细胞因子诱导,在体外模拟银屑病。通过qRT-PCR检测XIST和miR-338-5p水平。采用CCK-8检测不同处理下细胞活力。ELISA法检测炎症因子浓度。荧光素酶报告基因测定证实了两者之间的调控关系。结果:银屑病患者血清XIST水平升高,根据受试者工作特征曲线可将银屑病患者与健康对照区分开。高水平的XIST与银屑病患者PASI评分及血清肿瘤坏死因子-α (TNF-α)、白细胞介素- 17a [IL-17A]、IL-22浓度呈正相关。沉默XIST可抑制m5诱导的角化细胞增殖,抑制炎症因子(TNF-α、IL-17A、IL-22)和趋化因子(CXCL1、CXCL8、CCL20)的分泌。XIST可“海绵”miR-338-5p, miR-338-5p下调可消除XIST沉默对细胞增殖和炎症的抑制作用。miR-338-5p在银屑病患者的临床血清样本中高表达。证实了miR-338-5p与IL-6的靶标关系。结论:LncRNA XIST在银屑病患者血清中高表达,且与病情严重程度、炎症程度呈正相关。XIST可能通过调节miR-338-5p/IL-6轴调控角质细胞增殖和炎症。
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引用次数: 3
Front & Back Matter 正面和背面事项
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-03-01 DOI: 10.1159/000523930
J. Fluhr, M. Lane
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引用次数: 0
An Exploratory Study of the Effects of the pH of Synthetic Urine on Skin Integrity in Healthy Participants. 合成尿液pH值对健康受试者皮肤完整性影响的探索性研究。
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-01-01 Epub Date: 2022-01-28 DOI: 10.1159/000522289
Sofoklis Koudounas, Dan L Bader, David Voegeli

Background: Incontinence-associated dermatitis (IAD) develops from prolonged exposure of skin to urine and/or stool and represents a common complication in older adults, reducing the quality of life. Increased pH is an important etiologic factor of IAD; however, the relationship between urinary pH and skin barrier disruption remains unclear.

Objective: The aim of this study is to examine the effects of synthetic urine (s-urine) at various pHs on transepidermal water loss (TEWL), stratum corneum hydration (SCH), and skin surface pH.

Methods: S-urine solutions (pH 5.0-9.0) were applied to the volar forearms of 15 healthy participants for 2 h, with another site serving as the untreated control. Measurements of TEWL, SCH, and skin surface pH were obtained at baseline (BL) and after each challenge. Skin buffering capacity was also examined in 5 volunteers by recording skin pH at BL, after 2 h exposure and every 5 min for 40 min.

Results: TEWL and SCH were increased following exposure to s-urine compared to BL values. Although there was a tendency for pH to increase after exposure, further investigation showed that changes are only temporal as pH value is restored to BL within 5 mins. There were no significant differences between solutions.

Conclusions: This study revealed that urine disrupts healthy skin integrity; however, its effects are not pH dependent. Transient changes were observed on the acid mantle of the skin due to its innate buffering capacity. Future studies need to examine the effects of urine combined with bacteria responsible for pH elevation in patients with urinary incontinence.

背景:尿失禁相关性皮炎(IAD)发生于皮肤长期暴露于尿液和/或粪便中,是老年人常见的并发症,降低了生活质量。pH值升高是IAD的重要病因;然而,尿液pH值与皮肤屏障破坏之间的关系尚不清楚。目的:本研究旨在探讨不同pH值的合成尿(s-urine)对经皮失水(TEWL)、角质层水化(SCH)和皮肤表面pH的影响。方法:将pH值为5.0-9.0的s-尿液溶液应用于15名健康受试者的前臂掌侧2小时,另一个部位作为未处理的对照组。在基线(BL)和每次刺激后测量TEWL、SCH和皮肤表面pH。5名志愿者的皮肤缓冲能力也通过记录皮肤pH值,在暴露2小时后,每5分钟,持续40分钟。结果:与BL值相比,暴露s尿后TEWL和SCH增加。虽然暴露后pH值有升高的趋势,但进一步的研究表明,这种变化只是暂时的,pH值在5分钟内恢复到BL。解决方案之间没有显著差异。结论:这项研究表明,尿液会破坏健康皮肤的完整性;然而,它的效果不依赖于pH值。由于其固有的缓冲能力,在皮肤的酸性膜上观察到短暂的变化。未来的研究需要检查尿与细菌联合对尿失禁患者pH值升高的影响。
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引用次数: 3
Metformin Promotes the Hair-Inductive Activity of Three-Dimensional Aggregates of Epidermal and Dermal Cells Self-Assembled in vitro. 二甲双胍促进体外自组装表皮和真皮细胞三维聚集体的毛发诱导活性。
IF 2.7 4区 医学 Q2 DERMATOLOGY Pub Date : 2022-01-01 Epub Date: 2021-12-09 DOI: 10.1159/000521400
Chao Sun, Shuang-Hai Hu, Bing-Qi Dong, Shan Jiang, Fang Miao, Tie-Chi Lei

Introduction: Although it has been reported that the antidiabetic drug metformin has multiple extra-hypoglycemic activities, such as anti-oxidation, antiaging, and even antitumor, topical metformin also can induce hair regeneration, but the precise mechanism involved in that process is still unclear.

Objectives: The aim of this study was to assess the effect of metformin on hair growth in a mouse hair-follicle reconstitution model generated by in vitro self-assembled three-dimensional aggregates of epidermal and dermal cells (DCs) (3D aggregates).

Methods: Epidermal cells and DCs were isolated and cultured from the mouse skin of 50 C57BL/6 mouse pups (1-day-old). For tracing the distribution of DCs during the self-assembly process of 3D aggregates, the DCs were labeled with Vybrant Dil Cell-Labeling Solution and mixed with epidermal cells at a 1:1 ratio. Formed 3D aggregates were treated with 10 mM metformin and then were grafted into recipient BALB/c nude mice. The biomarkers (hepatocyte growth factor [HGF], prominin-1 [CD133], alkaline phosphatase [ALP], β-catenin, and SRY-box transcription factor 2 [SOX2]) associated with the hair-inductive activity of DCs were detected in the grafted skin tissues and in cultured 3D aggregates treated with metformin using immunofluorescent staining, quantitative real-time RT-PCR (qRT-PCR), and Western blotting. Furthermore, the expression levels of CD133 were also examined in DCs with different passage numbers using qRT-PCR and Western blotting.

Results: Metformin directly stimulates the activity of ALP of cultured 3D aggregates, upregulates both the protein and mRNA expression levels of molecular markers (HGF, CD133, ALP, β-catenin, and SOX2), and improves the survival rate of reconstituted hair follicles. Moreover, we also found that metformin increases the expression of CD133 in DCs thus maintaining their trichogenic capacity that would normally be lost by serial subculture.

Conclusions: These results suggest that metformin can promote hair follicle regeneration in vitro through upregulation of the hair-inductive capability of DCs, warranting further evaluation in the clinical treatment of male or female pattern hair loss.

导读:降糖药二甲双胍虽然有报道称具有抗氧化、抗衰老、甚至抗肿瘤等多种额外降糖活性,但外用二甲双胍也能诱导头发再生,但其具体机制尚不清楚。目的:本研究的目的是评估二甲双胍对小鼠毛囊重建模型的影响,该模型是由体外自组装的表皮和真皮细胞三维聚集体(dc) (3D聚集体)构建的。方法:从50只1日龄C57BL/6小鼠皮肤中分离培养表皮细胞和树突状细胞。为了追踪dc在3D聚集体自组装过程中的分布,用Vybrant Dil细胞标记液对dc进行标记,并以1:1的比例与表皮细胞混合。将形成的3D聚集体用10 mM二甲双胍处理后,移植到BALB/c受体裸鼠体内。采用免疫荧光染色、定量实时RT-PCR (qRT-PCR)和Western blotting检测移植皮肤组织和经二甲双胍处理的3D聚集体中与DCs致发活性相关的生物标志物(肝细胞生长因子[HGF]、pronin -1 [CD133]、碱性磷酸酶[ALP]、β-catenin和SRY-box转录因子2 [SOX2])。此外,利用qRT-PCR和Western blotting检测不同传代数的dc中CD133的表达水平。结果:二甲双胍直接刺激培养的3D聚集体的ALP活性,上调分子标志物(HGF、CD133、ALP、β-catenin、SOX2)的蛋白和mRNA表达水平,提高重建毛囊的存活率。此外,我们还发现二甲双胍增加了dc中CD133的表达,从而维持了它们在连续传代培养中通常会失去的生毛能力。结论:二甲双胍可通过上调树突状细胞的致发能力促进体外毛囊再生,值得在临床治疗男性或女性型脱发中进一步评估。
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引用次数: 5
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Skin Pharmacology and Physiology
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