Background

Fibroblast dysfunction is the main pathogenic mechanism of idiopathic pulmonary fibrosis (IPF). S100 calcium-binding protein A4 (S100A4) plays critical roles in the proliferation of fibroblasts and in the development of pulmonary, hepatic, and renal fibrosis. However, the clinical implications of S100A4 in IPF have not been evaluated.

Methods and materials

The S100A4 mRNA and protein levels were measured by real-time PCR and immunoblotting in fibroblasts from IPF patients and controls. The S100A4 level was measured by enzyme-linked immunosorbent assay in bronchoalveolar lavage fluid (BALF) from the normal controls (NCs; n = 33) and from patients with IPF (n = 87), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 19), and sarcoidosis (n = 9). S100A4 localization was evaluated by immunofluorescence staining.

Results

The S100A4 mRNA and protein levels were significantly higher in fibroblasts from IPF patients (n = 14) than in those from controls (n = 10, p < 0.001). The S100A4 protein level in BALF was significantly higher in the IPF (89.25 [49.92–203.02 pg/mL]), NSIP (74.53 [41.88–131.45 pg/mL]), HP (222.36 [104.92–436.92 pg/mL]) and sarcoidosis (101.62 [59.36–300.62 pg/mL]) patients than in the NCs (7.57 [1.31–14.04 pg/mL], p < 0.01, respectively). Cutoff S100A4 levels of 18.85 and 28.88 pg/mL had 87.4% and 87.8% accuracy, respectively, for discriminating IPF and other lung diseases from NCs.

Conclusions

S100A4 is expressed by α-SMA-positive cells in the interstitium of the IPF patients. S100A4 may participate in the development of IPF, and its protein level may be a candidate diagnostic and therapeutic marker for IPF.

中文翻译：

---

特发性肺纤维化患者的肺中S100钙结合蛋白A4水平升高。

背景

成纤维细胞功能障碍是特发性肺纤维化（IPF）的主要致病机制。S100钙结合蛋白A4（S100A4）在成纤维细胞的增殖以及肺，肝和肾纤维化的发展中起关键作用。但是，尚未评估S100A4在IPF中的临床意义。

方法和材料

通过实时PCR和免疫印迹法检测IPF患者和对照组成纤维细胞中的S100A4 mRNA和蛋白水平。S100A4水平通过酶联免疫吸附法在正常对照组（NCs; n = 33）和IPF患者（n = 87），非特异性间质性肺炎（NSIP; n =）的支气管肺泡灌洗液（BALF）中进行测量22），过敏性肺炎（HP； n = 19）和结节病（n = 9）。通过免疫荧光染色评估S100A4的定位。

结果

IPF患者（n = 14）的成纤维细胞中的S100A4 mRNA和蛋白水平显着高于对照组（n = 10，p <0.001）。IPF（89.25 [49.92–203.02 pg / mL]），NSIP（74.53 [41.88–131.45 pg / mL]），HP（222.36 [104.92–436.92 pg / mL]）和BALF中BALF中的S100A4蛋白水平明显更高。结节病（101.62 [59.36–300.62 pg / mL]）患者比NCs（7.57 [1.31–14.04 pg / mL]，p <0.01）。用于区分IPF和其他肺部疾病与NCs的临界值S100A4的准确度分别为18.85和28.88 pg / mL，准确度分别为87.4％和87.8％。

结论

S100A4由IPF患者间质中的α-SMA阳性细胞表达。S100A4可能参与IPF的发展，其蛋白水平可能是IPF的候选诊断和治疗标记。