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层状上皮中半乳糖凝集素-7 表达减少可能有助于系统性硬皮病皮肤和食管表现的发生。

A potential contribution of decreased galectin-7 expression in stratified epithelia to the development of cutaneous and oesophageal manifestations in systemic sclerosis.

机构信息

Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.

出版信息

Exp Dermatol. 2019 May;28(5):536-542. doi: 10.1111/exd.13900.

DOI:10.1111/exd.13900
PMID:30739341
Abstract

BACKGROUNDS

Stratified epithelia have caught much attention as potential contributors to the development of dermal and oesophageal fibrosis in systemic sclerosis (SSc). Galectin-7 is a marker of all types of stratified epithelia, which is involved in the maintenance of epidermal homeostasis. So far, the role of galectin-7 has not been studied in SSc.

OBJECTIVES

To investigate the potential contribution of galectin-7 to the development of clinical manifestations in SSc.

METHODS

Galectin-7 expression was examined in skin samples and cultured keratinocytes by immunostaining and/or quantitative reverse transcription PCR. Serum galectin-7 levels were determined by enzyme-linked immunosorbent assay in 63 SSc and 20 healthy subjects.

RESULTS

Galectin-7 expression was markedly decreased in the epidermis of SSc lesional skin compared with that of healthy control skin. Serum galectin-7 levels were significantly lower in SSc patients than in healthy controls and inversely correlated with skin score. In addition, SSc patients with diffuse pigmentation and those with oesophageal dysfunction had significantly decreased serum galectin-7 levels as compared to those without each symptom. Importantly, endothelin-1 stimulation suppressed galectin-7 expression in normal human keratinocytes, and bosentan, a dual endothelin receptor antagonist, reversed circulating galectin-7 levels and epidermal galectin-7 expression in SSc patients.

CONCLUSIONS

Galectin-7 downregulation in stratified epithelia, which is mediated at least partially by autocrine endothelin stimulation, may contribute to the development of cutaneous manifestations and oesophageal dysfunction in SSc patients.

摘要

背景

分层上皮作为皮肤和食管纤维化系统性硬化症(SSc)的潜在来源,已引起广泛关注。半乳糖凝集素-7 是所有类型分层上皮的标志物,参与表皮的稳态维持。迄今为止,半乳糖凝集素-7 在 SSc 中的作用尚未得到研究。

目的

研究半乳糖凝集素-7 是否可能对 SSc 临床表现的发展有影响。

方法

通过免疫染色和/或定量逆转录 PCR 检查皮肤样本和培养的角质形成细胞中的半乳糖凝集素-7 表达。采用酶联免疫吸附试验测定 63 例 SSc 和 20 例健康对照者的血清半乳糖凝集素-7 水平。

结果

与健康对照皮肤相比,SSc 皮损皮肤的表皮中半乳糖凝集素-7 表达明显降低。SSc 患者的血清半乳糖凝集素-7 水平明显低于健康对照组,且与皮肤评分呈负相关。此外,与无该症状的患者相比,弥漫性色素沉着和食管功能障碍的 SSc 患者的血清半乳糖凝集素-7 水平显著降低。重要的是,内皮素-1 刺激可抑制正常人角质形成细胞中的半乳糖凝集素-7 表达,而内皮素受体双重拮抗剂波生坦可逆转 SSc 患者的循环半乳糖凝集素-7 水平和表皮半乳糖凝集素-7 表达。

结论

至少部分通过自分泌内皮素刺激的分层上皮中半乳糖凝集素-7 的下调可能导致 SSc 患者的皮肤表现和食管功能障碍的发展。

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