Baños-Hernández Christian Johana, Bucala Richard, Hernández-Bello Jorge, Navarro-Zarza José Eduardo, Villanueva-Pérez Martha Arisbeth, Godínez-Rubí Marisol, Parra-Rojas Isela, Vázquez-Villamar Mirna, Pereira-Suárez Ana Laura, Muñoz Valle José Francisco
Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo de los Bravo, Guerrero, México.
Cent Eur J Immunol. 2021;46(3):375-383. doi: 10.5114/ceji.2021.109756. Epub 2021 Oct 8.
Macrophage migration inhibitory factor (MIF) has been associated with the pathogenesis of several rheumatic diseases. In systemic sclerosis (SSc) it has been shown that MIF expression is dysregulated in serum and skin. However, the MIF receptor, CD74, has been poorly investigated and its potential role in the pathogenesis of SSc remains unknown. This study aimed to analyze mRNA, tissue, and serum expression of MIF and CD74 in patients with limited (lcSSc) and diffuse (dcSSc) systemic sclerosis. A case-control study in 20 SSc patients and 20 control subjects (CS) from southern México was conducted. MIF and CD74 mRNA expression levels were quantified by real-time PCR, MIF serum levels were measured by an ELISA kit, and MIF and its receptor CD74 were evaluated by immunohistochemistry of skin biopsies. MIF mRNA expression was significantly higher in CS than in SSc patients (p = 0.02), while CD74 showed no differences between patients and CS. MIF serum levels were similar between SSc patients and CS: dcSSc = 3.82 ng/ml, lcSSc = 3.57 ng/ml, and CS = 3.28 ng/ml. In skin biopsies of SSc, MIF and CD74 were enhanced in keratinocytes, while they showed decreased expression in endothelial cells. On the other hand, the staining of CD74 was high in fibroblasts of dcSSc patients. Our findings show MIF and CD74 deregulation at the transcriptional and translational levels in SSc, which might be associated with the proinflammatory process leading to tissue remodeling and excessive fibrosis in SSc.
巨噬细胞移动抑制因子（MIF）与多种风湿性疾病的发病机制相关。在系统性硬化症（SSc）中，已有研究表明血清和皮肤中的MIF表达失调。然而，MIF受体CD74的研究较少，其在SSc发病机制中的潜在作用仍不清楚。本研究旨在分析局限性（lcSSc）和弥漫性（dcSSc）系统性硬化症患者中MIF和CD74的mRNA、组织及血清表达情况。对来自墨西哥南部的20例SSc患者和20例对照受试者（CS）进行了病例对照研究。通过实时PCR定量MIF和CD74的mRNA表达水平，用ELISA试剂盒检测MIF血清水平，并通过皮肤活检的免疫组织化学评估MIF及其受体CD74。CS中MIF mRNA表达显著高于SSc患者（p = 0.02），而CD74在患者和CS之间无差异。SSc患者和CS的MIF血清水平相似：dcSSc = 3.82 ng/ml，lcSSc = 3.57 ng/ml，CS = 3.28 ng/ml。在SSc的皮肤活检中，角质形成细胞中MIF和CD74增强，而在内皮细胞中表达降低。另一方面，dcSSc患者成纤维细胞中CD74染色较高。我们的研究结果表明，SSc中MIF和CD74在转录和翻译水平上失调，这可能与导致SSc组织重塑和过度纤维化的促炎过程有关。
