Type V collagen (Col V) has the potential to become an autoantigen and has been associated with the pathogenesis of systemic sclerosis (SSc). We characterized serological, functional, and histopathological features of the skin and lung in a novel SSc murine model induced by Col V immunization. Female C57BL/6 mice (n = 19, IMU-COLV) were subcutaneously immunized with two doses of Col V (125 μg) emulsified in complete Freund adjuvant, followed by two intramuscular boosters. The control group (n = 19) did not receive Col V. After 120 days, we examined the respiratory mechanics, serum autoantibodies, and vascular manifestations of the mice. The skin and lung inflammatory processes and the collagen gene/protein expressions were analyzed. Vascular manifestations were characterized by endothelial cell activity and apoptosis, as shown by the increased expression of VEGF, endothelin-1, and caspase-3 in endothelial cells. The IMU-COLV mice presented with increased tissue elastance and a nonspecific interstitial pneumonia (NSIP) histologic pattern in the lung, combined with the thickening of the small and medium intrapulmonary arteries, increased Col V fibers, and increased COL1A1, COL1A2, COL3A1, COL5A1, and COL5A2 gene expression. The skin of the IMU-COLV mice showed thickness, epidermal rectification, decreased papillary dermis, atrophied appendages, and increased collagen, COL5A1, and COL5A2 gene expression. Anti-collagen III and IV and ANA antibodies were detected in the sera of the IMU-COLV mice. We demonstrated that cutaneous, vascular, and pulmonary remodeling are mimicked in the Col V-induced SSc mouse model, which thus represents a suitable preclinical model to study the mechanisms and therapeutic approaches for SSc.

中文翻译：

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提出在 C57BL/6 小鼠中使用 V 型胶原诱导的新型系统性硬化症动物模型，该模型可再现纤维化、血管病变和自身免疫。


V 型胶原蛋白 (Col V) 有可能成为自身抗原，并与系统性硬化症 (SSc) 的发病机制相关。我们在 Col V 免疫诱导的新型 SSc 小鼠模型中描述了皮肤和肺部的血清学、功能和组织病理学特征。雌性 C57BL/6 小鼠（n = 19，IMU-COLV）用两剂乳化在完全弗氏佐剂中的 Col V（125 μg）进行皮下免疫，然后进行两次肌内加强免疫。对照组（n = 19）不接受 Col V。120 天后，我们检查了小鼠的呼吸力学、血清自身抗体和血管表现。分析皮肤和肺部炎症过程以及胶原蛋白基因/蛋白质表达。血管表现的特征是内皮细胞活性和凋亡，如内皮细胞中 VEGF、内皮素-1 和 caspase-3 表达增加所示。 IMU-COLV 小鼠肺部组织弹性增加，出现非特异性间质性肺炎 (NSIP) 组织学模式，同时肺内小动脉和中动脉增厚，Col V 纤维增加，COL1A1、COL1A2、COL3A1、COL5A1 增加和 COL5A2 基因表达。 IMU-COLV小鼠的皮肤显示增厚、表皮矫正、真皮乳头减少、附属器萎缩、胶原蛋白、COL5A1和COL5A2基因表达增加。在 IMU-COLV 小鼠的血清中检测到抗 III 型和 IV 型胶原蛋白以及 ANA 抗体。我们证明，Col V 诱导的 SSc 小鼠模型可模拟皮肤、血管和肺部重塑，因此该模型代表了研究 SSc 机制和治疗方法的合适临床前模型。