Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, 221006, Jiangsu, China.
Department of Thoracic and Cardiovascular Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Respir Res. 2022 Apr 22;23(1):100. doi: 10.1186/s12931-022-02027-4.
Idiopathic pulmonary fibrosis (IPF) is a highly heterogeneous and fatal lung disease. In addition to dense fibrous tissue, abnormal angiogenesis is also an important feature of IPF. Pigment epithelium-derived factor (PEDF) is an angiogenesis inhibitor and a potential anti-fibrous factor. The purpose of this experiment is to observe the effect of PEDF on bleomycin (BLM)-induced pulmonary fibrosis in rats.
In vivo, pathological examination and detection of related factors were performed on pulmonary fibrosis induced by BLM in rats, and the temporal and spatial distribution of PEDF was investigated. Furthermore, lung gene delivery (PEDF-adeno-associated virus) was performed to investigate the effect of PEDF on pulmonary fibrosis. In vitro, lentiviral vectors were used to construct PEDF over-expression or knock out primary rat lung (PRL) fibroblasts. The effect of PEDF on fibroblast activation under TGF-β1 stimulation was evaluated, and the activation of TGF-β1/smad pathway and PPAR-γ expression (in the presence or absence of PPAR-γ inhibitors) were analyzed.
In vivo results showed that PEDF expression decreased during the inflammatory phase and increased during the fibrotic phase. PEDF could inhibit the progression of pulmonary fibrosis in rats. In vitro results showed that PEDF could effectively inhibit TGF-β1-stimulated fibroblast activation and reduce the production of α-SMA and collagen-I. PEDF could inhibit the TGF-β1/smad pathway by up-regulating the activity of PPAR-γ.
PEDF can act as an anti-fibrotic factor, inhibit fibroblast activation by upregulating PPAR-γ activity and reduce BLM-induced pulmonary fibrosis in rats.
特发性肺纤维化（IPF）是一种高度异质性和致命的肺部疾病。除了致密的纤维组织外，异常的血管生成也是 IPF 的一个重要特征。色素上皮衍生因子（PEDF）是一种血管生成抑制剂，也是一种潜在的抗纤维化因子。本实验旨在观察 PEDF 对博来霉素（BLM）诱导的大鼠肺纤维化的影响。
在体内，通过 BLM 诱导大鼠肺纤维化进行病理学检查和相关因素检测，研究 PEDF 的时空分布。此外，进行肺基因传递（PEDF-腺相关病毒），以研究 PEDF 对肺纤维化的影响。在体外，使用慢病毒载体构建 PEDF 过表达或敲除原代大鼠肺（PRL）成纤维细胞。评估 PEDF 在 TGF-β1 刺激下对成纤维细胞激活的影响，并分析 TGF-β1/smad 通路和 PPAR-γ 表达的激活（在存在或不存在 PPAR-γ 抑制剂的情况下）。
体内结果表明，PEDF 表达在炎症期下降，在纤维化期增加。PEDF 可抑制大鼠肺纤维化的进展。体外结果表明，PEDF 可有效抑制 TGF-β1 刺激的成纤维细胞激活，减少α-SMA 和胶原-I 的产生。PEDF 可通过上调 PPAR-γ 的活性抑制 TGF-β1/smad 通路。
PEDF 可作为一种抗纤维化因子，通过上调 PPAR-γ 的活性抑制成纤维细胞的激活，减少 BLM 诱导的大鼠肺纤维化。
