Pulmonary fibrosis is a progressive lung disease characterized by myofibroblast accumulation and excessive extracellular matrix deposition. We sought to investigate the role of FKBP13 (13-kD FK506-binding protein), an endoplasmic reticulum–resident molecular chaperone, in various forms of pulmonary fibrosis. We first characterized the gene and protein expression of FKBP13 in lung biopsy specimens from 24 patients with idiopathic pulmonary fibrosis and 17 control subjects. FKBP13 expression was found to be elevated in the fibrotic regions of idiopathic pulmonary fibrosis lung tissues and correlated with declining forced vital capacity and dyspnea severity. FKBP13 expression was also increased in lung biopsy specimens of patients with hypersensitivity pneumonitis, rheumatoid arthritis, and sarcoidosis-associated interstitial lung disease. We next evaluated the role of this protein using FKBP13^−/− mice in a bleomycin model of pulmonary fibrosis. Animals were assessed for lung function and histopathology at different stages of lung injury including the inflammatory (Day 7), fibrotic (Day 21), and resolution (Day 50) phases. FKBP13^−/− mice showed increased infiltration of inflammatory cells and cytokines at Day 7, increased lung elastance and fibrosis at Day 21, and impaired resolution of fibrosis at Day 50. These changes were associated with an increased number of cells that stained positive for TUNEL and cleaved caspase 3 in the FKBP13^−/− lungs, indicating a heightened cellular sensitivity to bleomycin. Our findings suggest that FKBP13 is a potential biomarker for severity of interstitial lung diseases and that it has a biologically relevant role in protecting mice against bleomycin-induced injury, inflammation, and fibrosis.

肺纤维化是一种以肌成纤维细胞聚集和细胞外基质过度沉积为特征的进行性肺部疾病。我们试图研究 FKBP13（13-kD FK506 结合蛋白），一种内质网驻留分子伴侣，在各种形式的肺纤维化中的作用。我们首先对 24 名特发性肺纤维化患者和 17 名对照受试者的肺活检标本中 FKBP13 的基因和蛋白表达进行了表征。FKBP13 表达在特发性肺纤维化肺组织的纤维化区域中升高，并与用力肺活量下降和呼吸困难严重程度相关。在过敏性肺炎、类风湿性关节炎和结节病相关间质性肺病患者的肺活检标本中，FKBP13 的表达也增加。^-/-肺纤维化博莱霉素模型中的小鼠。在肺损伤的不同阶段，包括炎症（第 7 天）、纤维化（第 21 天）和消退（第 50 天）阶段，评估动物的肺功能和组织病理学。FKBP13 ^-/-小鼠在第 7 天显示炎症细胞和细胞因子浸润增加，在第 21 天肺弹性和纤维化增加，在第 50 天纤维化消退受损。这些变化与 TUNEL 染色阳性细胞数量增加有关和 FKBP13 中裂解的半胱天冬酶 3 ^-/-肺，表明细胞对博来霉素的敏感性增加。我们的研究结果表明，FKBP13 是间质性肺疾病严重程度的潜在生物标志物，并且它在保护小鼠免受博莱霉素引起的损伤、炎症和纤维化方面具有生物学相关作用。