Potential role of insulin-like growth factor 1 and growth hormone in acneiform eruptions: evidence from a rat model of acromegaly.

IF 3.5 2区 医学 Q1 Medicine
Mengjie Fan, Yangfan Lai, Xiaoyao Fan, Yichang Yuan, Jin Chen, Yanzhuo Hu, Ye Liu, Min He, Meiyan Liu, Hongying Ye, Zhaoyun Zhang, Yongfei Wang, Leihong Xiang, Zhengyuan Chen, Ying Ma
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Abstract

Background: Acne, a chronic inflammatory disease, is influenced by insulin-like growth factor 1 (IGF-1). Acromegaly, characterized by excessive growth hormone (GH) and IGF-1, is associated with a higher prevalence of acne, though the underlying mechanisms remain unclear.

Objective: This study aims to explore the underlying mechanisms why patients with acromegaly are more susceptible to acne, especially refractory acne.

Methods: An acromegaly rat model was established via biweekly long-acting recombinant human GH (rhGH) injections for eight weeks. Serum levels of GH, IGF-1, and glucose were measured, and skin pathology was examined. Immunohistochemistry, transcriptomics, and proteomics were performed to explore molecular pathways, with RT-qPCR and western blot validation.

Results: Serum GH and IGF-1 levels significantly increased from week 3 and remained elevated throughout the study in the rhGH-treated group. Acneiform lesions, including epidermal hyperkeratosis, sebaceous gland hyperplasia, and dermal thickening, were observed. Immunohistochemical analysis revealed upregulation of IGF-1, IGF-1R, SREBP1, and IL-1β. Transcriptomic and proteomic analyses identified 1,112 differentially expressed genes and 440 differentially expressed proteins, underscoring the activation of inflammation, extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), and cell proliferation through PI3K/Akt pathways. Significant upregulation of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP-1) was observed in both transcriptomic and proteomic analyses.

Conclusion: Chronic GH stimulation leads to persistent IGF-1 elevation, promoting acne by increasing IGF-1R expression and disrupting ECM remodeling via PI3K/Akt-regulated MMPs and TIMP-1. These findings help clarify the link between acromegaly and acne and provide mechanistic insights into the role of IGF-1 in acne pathogenesis.

胰岛素样生长因子1和生长激素在痘状爆发中的潜在作用:来自肢端肥大症大鼠模型的证据。
背景:痤疮是一种慢性炎症性疾病,受胰岛素样生长因子1 (IGF-1)的影响。肢端肥大症以生长激素(GH)和IGF-1过多为特征,与较高的痤疮患病率相关,但其潜在机制尚不清楚。目的:探讨肢端肥大症患者易患痤疮,尤其是难治性痤疮的潜在机制。方法:采用双周注射长效重组人生长激素(rhGH)建立肢端肥大症大鼠模型,持续8周。测定血清GH、IGF-1和葡萄糖水平,并检查皮肤病理。采用免疫组织化学、转录组学和蛋白质组学方法探索分子通路,并采用RT-qPCR和western blot验证。结果:rhgh治疗组血清GH和IGF-1水平从第3周开始显著升高,并在整个研究过程中保持升高。观察到痤疮样病变,包括表皮角化过度,皮脂腺增生和真皮增厚。免疫组化分析显示IGF-1、IGF-1R、SREBP1和IL-1β上调。转录组学和蛋白质组学分析鉴定出1112个差异表达基因和440个差异表达蛋白,强调炎症激活、细胞外基质(ECM)重塑、上皮-间质转化(EMT)和通过PI3K/Akt通路的细胞增殖。转录组学和蛋白质组学分析均发现基质金属蛋白酶(MMPs)和金属蛋白酶1组织抑制剂(TIMP-1)显著上调。结论:慢性生长激素刺激导致持续的IGF-1升高,通过增加IGF-1R表达和通过PI3K/ akt调节的MMPs和TIMP-1破坏ECM重塑来促进痤疮。这些发现有助于阐明肢端肥大症和痤疮之间的联系,并为IGF-1在痤疮发病机制中的作用提供机制见解。
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来源期刊
Journal of Endocrinological Investigation
Journal of Endocrinological Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
8.10
自引率
7.40%
发文量
242
期刊介绍: The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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