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库欣综合征的皮肤分子变化及治疗效果。

Molecular skin changes in Cushing syndrome and the effects of treatment.

机构信息

Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey.

Erciyes University Genome and Stem Cell Institution, Kayseri, Turkey.

出版信息

J Endocrinol Invest. 2021 Jan;44(1):153-163. doi: 10.1007/s40618-020-01285-7. Epub 2020 May 14.

DOI:10.1007/s40618-020-01285-7
PMID:32410187
Abstract

OBJECTIVE

We investigated newly diagnosed patients with endogenous CS for molecular changes in skin by biopsy before and a year after treatment of CS.

PATIENTS AND METHODS

26 Patients with CS and 23 healthy controls were included. All the patients were evaluated before and a year after treatment. Skin biopsies were obtained from abdominal region before and a year after treatment in patients with CS and once from healthy volunteers. Total RNA was isolated from the skin biopsy samples and the real-time PCR system was used to determine the expression levels of 23 genes in the skin biopsy.

RESULTS

Skin expression levels of HAS 1, 2 and 3 mRNAs were lower and COL1A2, COL2A1, COL3A1 mRNAs were higher in patients with CS than in normal controls. MMP-9, TIMP-1 and elastin mRNA expression levels were similar in two groups. Skin IL-1β mRNA expression level was significantly higher in patients with CS. None of these parameters changed significantly 12 months after treatment. Patients with CS showed higher skin GH and HSD11B1 mRNA expressions and lower GHR and IGF-1R mRNA expression compared to control. Expression levels of IGF-1, GR and HSD11B2 mRNA were similar in two groups. None of these parameters changed significantly 12 months after treatment.

CONCLUSION

CS is associated with increased expression levels of skin COL1A2, COL2A1, COL3A1 mRNAs (which are correlated with increased expression level of skin GH mRNA). Decreased skin HAS may cause decreased synthesis of HA that contributes to thinning of skin in CS. Increased local inflammatory cytokine and HSD11B1 mRNAs may be related to the acne formation in CS. Treatment of CS was not able to reverse these changes and ongoing changes were detected after treatment.

摘要

目的

通过对 CS 治疗前后的皮肤活检,研究内源性 CS 新诊断患者的分子变化。

方法

纳入 26 例 CS 患者和 23 例健康对照者。所有患者均在治疗前和治疗 1 年后进行评估。CS 患者在治疗前和治疗 1 年后从腹部获取皮肤活检,健康志愿者仅取一次。从皮肤活检样本中分离总 RNA,采用实时 PCR 系统测定皮肤活检中 23 个基因的表达水平。

结果

CS 患者皮肤 HAS1、HAS2 和 HAS3mRNA 的表达水平较低,COL1A2、COL2A1 和 COL3A1mRNA 的表达水平较高。两组间 MMP-9、TIMP-1 和弹性蛋白 mRNA 表达水平相似。CS 患者皮肤 IL-1βmRNA 表达水平显著升高。治疗 12 个月后,这些参数均无明显变化。CS 患者皮肤 GH 和 HSD11B1mRNA 的表达水平较高,GHR 和 IGF-1RmRNA 的表达水平较低,而 IGF-1、GR 和 HSD11B2mRNA 的表达水平与对照组相似。治疗 12 个月后,这些参数均无明显变化。

结论

CS 与皮肤 COL1A2、COL2A1 和 COL3A1mRNA 表达水平升高有关(与皮肤 GHmRNA 表达水平升高相关)。皮肤 HAS 减少可能导致 HA 合成减少,导致 CS 患者皮肤变薄。局部炎症细胞因子和 HSD11B1mRNA 表达增加可能与 CS 痤疮形成有关。CS 治疗无法逆转这些变化,且在治疗后仍有持续变化。

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