Effect of Janus Kinase 3 Inhibitor on Sebaceous Gland Regeneration during Skin Wound Healing.

IF 1.5 4区 医学 Q3 DERMATOLOGY Annals of Dermatology Pub Date : 2023-08-01 DOI:10.5021/ad.22.204
Won Tae Jo, A Young Kim, Hyun Goo Woo, Hae Jun Song, Eun Joo Baik
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Abstract

Background: Janus kinase (Jak) 3 has recently been shown as a beneficial target for the treatment of chronic inflammatory diseases, such as psoriasis and alopecia areata. The role of Jak3 in tissue repair and remodeling is emerging.

Objective: This study aimed to investigate the role of Jak3 signaling in the remodeling of the sebaceous gland (SG) during skin wound repair, and the development of in vitro SGs.

Methods: Mouse skin tissue (ICR mouse) was obtained from the recovered skin eight days after a 4 mm biopsy punch wound. To observe the role of Jak3, the selective inhibitors WHI-p131 and PF06651600 was administered. Formation of in vitro SG was examined using primary sebocyte cultures obtained postnatally from 3-day-old mice.

Results: The data showed that SGs showed highly positive signals with anti-isolectin B4, which also used for detection of angiogenetic vessels and the basal epidermis. Isolectin B4 could be a good indicator of SGs. The Jak3 inhibitors significantly reduced the area and volume of SG remodeling with reduced expression of p-Jak3. In addition, the area of cultured intact SG in vitro was significantly decreased in a concentration-dependent manner by Jak3 inhibition.

Conclusion: These data showed that Jak3 signaling is a potent regulator to develop SGs. Jak3 inhibition did not decrease the number of sebocytes in SGs but decreased the area and volume of SG remodeling. Therefore, Jak3 inhibition may be a potential target for the treatment of SG hyperplasia and associated skin diseases.

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Janus激酶3抑制剂对皮肤创面愈合中皮脂腺再生的影响。
背景:Janus激酶(Jak) 3最近被证明是治疗慢性炎症性疾病(如牛皮癣和斑秃)的有益靶点。Jak3在组织修复和重塑中的作用正在逐渐显现。目的:探讨Jak3信号通路在皮肤创面修复过程中皮脂腺(SG)重塑及体外皮脂腺(SG)形成中的作用。方法:取4 mm穿刺活检创面后8 d的皮肤组织(ICR小鼠)。为了观察Jak3的作用,给药选择性抑制剂WHI-p131和PF06651600。利用3日龄小鼠出生后获得的原代皮脂细胞培养物检测体外SG的形成。结果:SGs对抗分离素B4具有高度阳性信号,也可用于血管生成血管和基底表皮的检测。分离素B4可作为SGs的良好指标。Jak3抑制剂显著减少SG重塑的面积和体积,降低p-Jak3的表达。此外,体外培养的完整SG的面积因Jak3抑制而呈浓度依赖性显著减少。结论:这些数据表明Jak3信号是发生SGs的有效调控因子。Jak3抑制没有减少SG中脂细胞的数量,但减少了SG重塑的面积和体积。因此,Jak3抑制可能是治疗SG增生和相关皮肤病的潜在靶点。
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来源期刊
Annals of Dermatology
Annals of Dermatology 医学-皮肤病学
CiteScore
1.60
自引率
6.20%
发文量
77
审稿时长
6-12 weeks
期刊介绍: Annals of Dermatology (Ann Dermatol) is the official peer-reviewed publication of the Korean Dermatological Association and the Korean Society for Investigative Dermatology. Since 1989, Ann Dermatol has contributed as a platform for communicating the latest research outcome and recent trend of dermatology in Korea and all over the world. Ann Dermatol seeks for ameliorated understanding of skin and skin-related disease for clinicians and researchers. Ann Dermatol deals with diverse skin-related topics from laboratory investigations to clinical outcomes and invites review articles, original articles, case reports, brief reports and items of correspondence. Ann Dermatol is interested in contributions from all countries in which good and advanced research is carried out. Ann Dermatol willingly recruits well-organized and significant manuscripts with proper scope throughout the world.
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