Institute of Biochemistry and Cell Biology, National Research Council (IBBC-CNR), Department of Sense Organs, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy.
Department of Internal Medicine and Medical Specialties, Rheumatology Unit, Sapienza University of Rome, Viale del Policlinico 155, 00185 Rome, Italy.
Cells. 2023 May 9;12(10):1347. doi: 10.3390/cells12101347.
Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome. We confirmed a quantitative decrease in the amount of SP in the MSG of pSS patients and demonstrated a significant increase in NK1R levels compared with sicca subjects, indicating the involvement of SP fibers and NK1R in the impaired salivary secretion observed in pSS patients. Moreover, the increase in apoptosis (PARP-1 cleavage) in pSS patients was shown to be related to JNK phosphorylation. Since there is no satisfactory therapy for the treatment of secretory hypofunction in pSS patients, the SP pathway may be a new potential diagnostic tool or therapeutic target.
原发性干燥综合征（pSS）是一种系统性自身免疫性疾病，主要攻击泪腺和唾液腺，导致分泌功能受损，表现为口干和眼干。研究表明，pSS 患者的唾液腺神经支配受损，循环中的神经肽水平发生改变，这些神经肽被认为是唾液分泌减少的原因之一，包括 P 物质（SP）。我们通过 Western blot 分析和免疫荧光研究，比较了 pSS 患者和特发性干燥综合征患者的小唾液腺（MSG）活检组织中 SP 及其首选 G 蛋白偶联 TK 受体 1（NK1R）和凋亡标志物的表达水平。我们证实了 pSS 患者 MSG 中 SP 含量的定量减少，并证明与干燥综合征患者相比，NK1R 水平显著增加，表明 SP 纤维和 NK1R 参与了 pSS 患者观察到的唾液分泌受损。此外，pSS 患者的凋亡（PARP-1 裂解）增加与 JNK 磷酸化有关。由于目前尚无治疗 pSS 患者分泌功能低下的满意疗法，因此 SP 途径可能成为一种新的潜在诊断工具或治疗靶点。
