Khedr Ahmed Mb, Shaker Olfat G, El-Komy Mohamed Hm, Badr Amul M, Erfan Randa
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Helwan University, Ain Helwan, Cairo, Egypt.
Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Noncoding RNA Res. 2023 Dec 20;9(1):253-261. doi: 10.1016/j.ncrna.2023.12.003. eCollection 2024 Mar.
Systemic sclerosis (SSc) is a common autoimmune disorder involving the skin, blood vessels, and internal organs with an elusive pathophysiology. SSc is believed to be a genetically prone T-cell-mediated autoimmune disease. miRNAs and lncRNAs were thought to be involved in the etiology of several immunological diseases including SSc. This work aimed to assess the expression of miRNA-133, lncRNA-H19, PKM2, and TGF-β levels in SSc in comparison to controls and their relationship to the clinical course and severity of disease.
Fifty patients with SSc and 40 healthy age and sex-matched controls were included in this study. miRNA-133 and H19 expression levels were detected using quantitative RT-PCR while serum levels of PKM2 and TGF-β were measured using ELISA techniques. Patients' clinical data and treatments received were extracted and correlated with proteins investigated.
Our results showed that miRNA-133 was significantly downregulated in SSc patients in comparison to controls (Mean + SD of SSc = 0.61 ± 0.22, Mean ± SD of HC = 0.97 ± 0.007, p = 0.003). However, there was significant upregulation of the serum expressions of all other tested biomarkers in SSc patients in comparison to controls; H19 (Mean + SD of SSc = 10.37 ± 3.13, Mean ± SD of HC = 1.01 ± 0.01, p = 0.0001), PKM2 (Mean + SD of SSc = 28.0 ± 4.84, Mean ± SD of HC = 16.19 ± 1.32, p = 0.005) and TGF-β (Mean + SD of SSc = 150.8 ± 6.36, Mean ± SD of HC = 23.83 ± 0.93, p = 0.0001). We also detected several correlations between serum levels of the investigated proteins in patients with SSc.
Along with TGF-β, our results show that miRNA-133, H19, and PKM2 seem to be potential contributors to SSc pathogenesis and could be promising biomarkers in the diagnosis of SSc patients. The lncRNA-H19 correlations with TGF- β, miRNA-133, and PKM2 suggest a possible influential effect of this RNA molecule on the pathogenesis of SSc.
系统性硬化症（SSc）是一种常见的自身免疫性疾病，累及皮肤、血管和内脏器官，其病理生理学尚不清楚。SSc被认为是一种具有遗传易感性的T细胞介导的自身免疫性疾病。微小RNA（miRNA）和长链非编码RNA（lncRNA）被认为参与了包括SSc在内的多种免疫性疾病的病因。本研究旨在评估与对照组相比，SSc患者中miRNA-133、lncRNA-H19、丙酮酸激酶M2（PKM2）和转化生长因子-β（TGF-β）的水平，以及它们与疾病临床病程和严重程度的关系。
本研究纳入了50例SSc患者和40例年龄、性别匹配的健康对照。采用定量逆转录聚合酶链反应（RT-PCR）检测miRNA-133和H19的表达水平，采用酶联免疫吸附测定（ELISA）技术检测血清中PKM2和TGF-β的水平。提取患者的临床资料和接受的治疗，并与所研究的蛋白质进行相关性分析。
我们的结果显示，与对照组相比，SSc患者中miRNA-133显著下调（SSc组均值±标准差=0.61±0.22，健康对照组均值±标准差=0.97±0.007，p=0.003）。然而，与对照组相比，SSc患者中所有其他检测的生物标志物血清表达均显著上调；H19（SSc组均值±标准差=10.37±3.13，健康对照组均值±标准差=1.01±0.01，p=0.0001）、PKM2（SSc组均值±标准差=28.0±4.84，健康对照组均值±标准差=16.19±1.32，p=0.005）和TGF-β（SSc组均值±标准差=150.8±6.36，健康对照组均值±标准差=23.83±0.93，p=0.0001）。我们还检测到SSc患者血清中所研究蛋白质水平之间的几种相关性。
与TGF-β一样，我们的结果表明，miRNA-133、H19和PKM2似乎是SSc发病机制的潜在促成因素，可能是诊断SSc患者的有前景的生物标志物。lncRNA-H19与TGF-β、miRNA-133和PKM2的相关性表明，这种RNA分子可能对SSc的发病机制有影响。
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