Toosendanin Restrains Idiopathic Pulmonary Fibrosis by Inhibiting ZEB1/CTBP1 Interaction.

BACKGROUND: Extensive deposition of extracellular matrix (ECM) in idiopathic pulmonary fibrosis (IPF) is due to hyperactivation and proliferation of pulmonary fibroblasts. However, the exact mechanism is not clear. OBJECTIVE: This study focused on the role of CTBP1 in lung fibroblast function, elaborated its regulation mechanism, and analyzed the relationship between CTBP1 and ZEB1. Meanwhile, the antipulmonary fibrosis effect and its molecular mechanism of Toosendanin were studied. METHODS: Human IPF fibroblast cell lines (LL-97A and LL-29) and normal fibroblast cell lines (LL-24) were cultured in vitro. The cells were stimulated with FCS, PDGF-BB, IGF-1, and TGF-ß1, respectively. BrdU detected cell proliferation. The mRNA expression of CTBP1 and ZEB1 was detected by QRT-PCR. Western blotting was used to detect the expression of COL1A1, COL3A1, LN, FN, and α-SMA proteins. An animal model of pulmonary fibrosis was established to analyze the effects of CTBP1 silencing on pulmonary fibrosis and lung function in mice. RESULTS: CTBP1 was up-regulated in IPF lung fibroblasts. Silencing CTBP1 inhibits growth factor-driven proliferation and activation of lung fibroblasts. Overexpression of CTBP1 promotes growth factor-driven proliferation and activation of lung fibroblasts. Silencing CTBP1 reduced the degree of pulmonary fibrosis in mice with pulmonary fibrosis. Western blot, CO-IP, and BrdU assays confirmed that CTBP1 interacts with ZEB1 and promotes the activation of lung fibroblasts. Toosendanin can inhibit the ZEB1/CTBP1protein interaction and further inhibit the progression of pulmonary fibrosis. CONCLUSION: CTBP1 can promote the activation and proliferation of lung fibroblasts through ZEB1. CTBP1 promotes lung fibroblast activation through ZEB1, thereby increasing excessive deposition of ECM and aggravating IPF. Toosendanin may be a potential treatment for pulmonary fibrosis. The results of this study provide a new basis for clarifying the molecular mechanism of pulmonary fibrosis and developing new therapeutic targets.

Application value of contrast-enhanced ultrasound in the diagnosis of peripheral pulmonary focal lesions.

INTRODUCTION: Peripheral pulmonary lesions are encountered frequently in clinical practice. Accurate diagnosis of these lesions is of great importance for clinicians. Ultrasound-guided lung tissue puncture is a reliable method for diagnosing these lesions. OBJECTIVES: To investigate the application value of contrast-enhanced ultrasound (CEUS) combined with rapid on-site evaluation (ROSE) in the diagnosis of peripheral pulmonary focal lesions. METHODS: Eighty patients enrolled from July 2020 to June 2021 were divided into two groups: a conventional ultrasound group and a CEUS group. Both groups underwent diagnostic procedures guided by ROSE to improve the success rate of puncture sampling. The success rates and complications in both groups were compared. The results for lesion enhancement, time taken for the contrast agent to reach the lesions (AT) and lung tissues (L-AT), and the difference between these times (∆AT) were compared in the CEUS group. RESULTS: The success rate of biopsy in the CEUS group was 97.62%, which was significantly higher than that in the conventional ultrasound group (84%; P < .05). Puncture complications did not occur in the CEUS group and occurred in 5.26% of the cases in the conventional ultrasound group, but the difference was not statistically significant (P > .05). A comparison of enhancement of benign lesions and malignant lesions in the CEUS group showed a statistically significant difference (P < .05). The difference between the AT and ∆AT of benign and malignant lesions was statistically significant (P <.05). The optimal threshold of ∆AT was 2.05 s. CONCLUSION: CEUS combined with ROSE is a very important approach for biopsy in the diagnosis of peripheral pulmonary focal lesions. CEUS has definite clinical value in the diagnosis of benign and malignant lung lesions.