Dermatology and Venereology Department, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Medical Biology Department, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Mol Biol Rep. 2024 Aug 24;51(1):933. doi: 10.1007/s11033-024-09782-1.
Patients prone to psoriasis suffer after a breakdown of the epidermal barrier and develop poorly healing lesions with abnormal proliferation of keratinocytes. Strong inflammatory reactions with genotoxicity (short telomeres) suggest impaired immune defenses with DNA damage repair response (DDR) in patients with psoriasis. Recent evidence indicates the existence of crosstalk mechanisms linking the DDR machinery and hormonal signaling pathways that cooperate to influence both progressions of many diseases and responses to treatment. The aim of this study was to clarify whether steroid biosynthesis and genomic stability markers are altered in parallel during the formation of psoriatic skin. Understanding the interaction of the steroid pathway and DNA damage response is crucial to addressing underlying fundamental issues and managing resulting epidermal barrier disruption in psoriasis.
Skin (Lesional, non-lesional) and blood samples from twenty psoriasis patients and fifteen healthy volunteers were collected. Real-Time-PCR study was performed to assess levels of known transcripts such as: estrogen (ESR1, ESR2), androgen (AR), glucocorticoid/mineralocorticoid receptors (NR3C1, NR3C2), HSD11B1/HSD11B2, and DNA damage sensors (SMC1A, TREX1, TREX2, SSBP3, RAD1, RAD18, EXO1, POLH, HUS1).
We found that ESR1, ESR2, HSD11B1, NR3C1, NR3C2, POLH, and SMC1A transcripts were significantly decreased and AR, TREX1, RAD1, and SSBP3 transcripts were increased dramatically in the lesional skin compared to skin samples of controls.
We found that the regulation of the steroidogenic pathway was disrupted in the lesional tissue of psoriasis patients and that a sufficient glucocorticoid and mineralocorticoid response did not form and the estrogen/androgen balance was altered in favour of androgens. We suggest that an increased androgen response in the presence of DDR increases the risk of developing psoriasis. Although this situation may be the cause or the consequence of a disruption of the epidermal barrier, our data suggest developing new therapeutic strategies.
患有银屑病倾向的患者在表皮屏障崩溃后会感到不适，并出现愈合不良的病变，角质形成细胞异常增殖。强烈的炎症反应伴有遗传毒性（端粒缩短）表明银屑病患者的免疫防御受损，存在 DNA 损伤修复反应（DDR）。最近的证据表明，存在 DDR 机制与激素信号通路之间的串扰机制，它们合作影响许多疾病的进展和对治疗的反应。本研究旨在阐明在银屑病皮肤形成过程中，类固醇生物合成和基因组稳定性标志物是否平行改变。了解类固醇途径和 DNA 损伤反应的相互作用对于解决潜在的根本问题和管理银屑病中导致的表皮屏障破坏至关重要。
收集 20 名银屑病患者和 15 名健康志愿者的皮肤（病变、非病变）和血液样本。进行实时 PCR 研究以评估已知转录物的水平，例如：雌激素（ESR1、ESR2）、雄激素（AR）、糖皮质激素/盐皮质激素受体（NR3C1、NR3C2）、HSD11B1/HSD11B2 和 DNA 损伤传感器（SMC1A、TREX1、TREX2、SSBP3、RAD1、RAD18、EXO1、POLH、HUS1）。
我们发现与对照组皮肤样本相比，ESR1、ESR2、HSD11B1、NR3C1、NR3C2、POLH 和 SMC1A 转录物在病变皮肤中显著降低，而 AR、TREX1、RAD1 和 SSBP3 转录物则显著增加。
我们发现类固醇生成途径的调节在银屑病患者的病变组织中受到干扰，并且没有形成足够的糖皮质激素和盐皮质激素反应，雌激素/雄激素平衡向雄激素倾斜。我们认为，在 DDR 存在的情况下，雄激素反应增加会增加患银屑病的风险。尽管这种情况可能是表皮屏障破坏的原因或后果，但我们的数据表明需要开发新的治疗策略。
