Chen Ruofei, Zhang Xiao, Shang Yifang, Zhang Huaixuan, Li Xiaolei, Dai Hanren, Shuai Zongwen
Department of Rheumatology and Immunology, the First Affiliated Hospital of Anhui Medical University, Hefei, China.
First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Immunol. 2025 Apr 9;16:1569605. doi: 10.3389/fimmu.2025.1569605. eCollection 2025.
Systemic lupus erythematosus (SLE) is a persistent autoimmune disorder marked by dysregulation of the immune system, resulting in extensive tissue inflammation and subsequent damage. Fibroblasts are essential contributors to the pathogenesis of SLE, particularly in driving the progression of tissue fibrosis and inflammation. Recent research has proposed that the GEM gene may regulate fibroblast activity in SLE. However, the precise molecular mechanisms through which GEM modulates fibroblast functions in the context of SLE are yet to be fully elucidated. Gaining insight into these mechanisms is crucial for uncovering potential therapeutic targets aimed at addressing fibrosis and inflammation associated with SLE.
Single-cell RNA sequencing was integrated with cell-based assays, such as quantitative reverse transcription PCR (qRT-PCR) and functional cellular experiments, to investigate the underlying mechanisms. The regulatory mechanisms of GEM in fibroblasts were analyzed through functional cell assays.
Differential gene expression in fibroblast subpopulations was identified through single-cell RNA sequencing, with GEM emerging as a key gene implicated in these alterations. Trajectory analysis indicated that GEM expression correlated with fibroblast proliferation and migration. Subsequent experiments confirmed that GEM regulates fibroblast viability and influences SLE disease progression through modulation of cell proliferation, migration, and apoptosis.
GEM is highly differentially expressed in fibroblast subpopulations within SLE, and its altered expression impacts fibroblast proliferation and migration. GEM may regulate fibroblast activity and apoptosis, potentially contributing to the progression of SLE.
系统性红斑狼疮（SLE）是一种持续性自身免疫性疾病，其特征为免疫系统失调，导致广泛的组织炎症及随后的组织损伤。成纤维细胞是SLE发病机制的重要促成因素，尤其是在推动组织纤维化和炎症进展方面。最近的研究提出，GEM基因可能调节SLE中成纤维细胞的活性。然而，在SLE背景下，GEM调节成纤维细胞功能的确切分子机制尚未完全阐明。深入了解这些机制对于揭示针对SLE相关纤维化和炎症的潜在治疗靶点至关重要。
将单细胞RNA测序与基于细胞的检测方法（如定量逆转录PCR（qRT-PCR）和功能性细胞实验）相结合，以研究潜在机制。通过功能性细胞实验分析GEM在成纤维细胞中的调控机制。
通过单细胞RNA测序确定了成纤维细胞亚群中的差异基因表达，GEM成为与这些改变相关的关键基因。轨迹分析表明，GEM表达与成纤维细胞增殖和迁移相关。随后的实验证实，GEM通过调节细胞增殖、迁移和凋亡来调节成纤维细胞活力并影响SLE疾病进展。
GEM在SLE的成纤维细胞亚群中高度差异表达，其表达改变影响成纤维细胞增殖和迁移。GEM可能调节成纤维细胞活性和凋亡，可能促成SLE的进展。
