Potential role of SIRT-1 and SIRT-3 as biomarkers for the diagnosis and prognosis of idiopathic pulmonary fibrosis

IF 4.7 2区医学 Q1 RESPIRATORY SYSTEM

Respiratory Research Pub Date : 2024-04-27 DOI:10.1186/s12931-024-02796-0

Fabio Perrotta, Vito D’Agnano, Domenica Francesca Mariniello, Giuseppe Castaldo, Maria Vitale, Mario Cazzola, Andrea Bianco, Filippo Scialò

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a debilitating and progressive lung disease of unknown aetiology, characterized by the relentless deposition of fibrotic tissue. Biomarkers may play a pivotal role as indicators of disease presence, progression, and treatment response. Sirtuins, a family of enzymes with ADP ribosyltransferase or deacetylase activity, have been implicated in several diseases, including pulmonary fibrosis. A cross-sectional, prospective, observational single-center study was conducted to investigate the potential role of serum SIRTs levels as biomarkers in patients with IPF. Demographic, clinical, and functional data and serological samples were collected from 34 patients with IPF followed at the Interstital Lung and Rare Diseases Outpatient Clinic of the Vanvitelli Pneumology Clinic, Monaldi Hospital, Naples, Italy and from 19 age-matched controls. Serum SIRT-1 levels were significantly reduced in IPF patients compared to controls (median IPF 667 [435–858] pg/mL versus controls 925 [794–1173] pg/mL; p < 0.001 ). In contrast, serum SIRT-3 levels were significantly increased in IPF patients compared to controls (median IPF 338 [230–500] pg/mL versus controls 154 [99.8–246] pg/mL; p < 0.001). There were no statistically significant differences in serum SIRT-6 and SIRT-7 levels between IPF and controls. In addition, we found a significant positive correlation between SIRT-1 and lung function parameters such as FEV1% (ϱ=0.417;p = 0.016), FVC% (ϱ=0.449;p = 0.009) and DLCO% (ϱ=0.393;p = 0.024), while a significant negative correlation was demonstrated between SIR-1 and GAP score, demonstrating a significant reduction in SIRT-1 in advanced Gender-Age-Physiology (GAP) stages 2–3 compared to GAP stage 1 (p = 0.008). This prospective, cross-sectional study showed that SIRT-1 was associated with lung function and IPF severity and that both SIRT-1 and SIRT-3 could be considered as potential biomarkers of IPF, whereas SIRT-6 and SIRT-7 were not associated with IPF.

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SIRT-1和SIRT-3作为特发性肺纤维化诊断和预后生物标志物的潜在作用

特发性肺纤维化（IPF）是一种使人衰弱的进行性肺部疾病，病因不明，其特征是纤维组织的无情沉积。生物标志物可作为疾病存在、进展和治疗反应的指标，发挥关键作用。Sirtuins是一个具有ADP核糖转移酶或去乙酰化酶活性的酶家族，与包括肺纤维化在内的多种疾病有关。一项横断面、前瞻性、观察性单中心研究旨在探讨血清 SIRTs 水平作为生物标志物在 IPF 患者中的潜在作用。研究人员收集了意大利那不勒斯莫纳尔迪医院 Vanvitelli 肺病诊所间肺病和罕见病门诊的 34 名 IPF 患者以及 19 名年龄匹配的对照组患者的人口统计学、临床和功能数据以及血清样本。与对照组相比，IPF患者的血清SIRT-1水平明显降低（IPF中位数为667 [435-858] pg/mL，对照组为925 [794-1173] pg/mL；P < 0.001）。相反，与对照组相比，IPF 患者的血清 SIRT-3 水平明显升高（中位数为 IPF 338 [230-500] pg/mL 对对照组 154 [99.8-246] pg/mL；p < 0.001）。IPF 与对照组之间的血清 SIRT-6 和 SIRT-7 水平差异无统计学意义。此外，我们发现 SIRT-1 与 FEV1%（ϱ=0.417;p = 0.016）、FVC%（ϱ=0.449;p = 0.009）和 DLCO%（ϱ=0.393;p = 0.024），而 SIR-1 与 GAP 评分之间呈显著负相关，表明与 GAP 1 期相比，晚期性别-年龄-生理学（GAP）2-3 期的 SIRT-1 显著降低（p = 0.008）。这项前瞻性横断面研究表明，SIRT-1 与肺功能和 IPF 严重程度相关，SIRT-1 和 SIRT-3 可被视为 IPF 的潜在生物标志物，而 SIRT-6 和 SIRT-7 与 IPF 无关。

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来源期刊

Respiratory Research 医学-呼吸系统

自引率

1.70%

发文量

314

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.