■特发性肺纤维化(IPF)是一种慢性和进行性间质性肺病,死亡率高,治疗效果有限。Nintedanib,酪氨酸激酶抑制剂,临床上用于治疗肺纤维化。目前,市场上只有尼达尼布用于治疗肺纤维化。帕唑帕尼是一种治疗肾细胞癌和晚期软组织肉瘤的药物。
■在这项研究中,我们探讨了帕唑帕尼是否可以减轻博莱霉素(BLM)诱导的肺纤维化,并探讨了其抗纤维化机制。进行了体内和体外研究,以研究帕唑帕尼在肺纤维化中的功效和作用机制。
■体内实验表明,帕唑帕尼可以减轻BLM引起的肺纤维化,降低胶原沉积程度,改善肺功能。体外实验表明,帕唑帕尼抑制转化生长因子-β1(TGF-β1)诱导的肌成纤维细胞活化,促进肌成纤维细胞凋亡和自噬。进一步的机制研究表明,帕唑帕尼在成纤维细胞活化过程中抑制了TGF-β1/Smad和非Smad信号通路。
■总而言之,帕唑帕尼通过抑制TGF-β1信号通路减轻BLM诱导的肺纤维化。帕唑帕尼抑制肌成纤维细胞活化,迁移,自噬,凋亡,通过下调TGF-β1/Smad信号途径和TGF-β1/non-Smad信号途径来建立细胞外基质(ECM)。它具有与尼达尼布相同的靶标,并且是酪氨酸激酶抑制剂。
UNASSIGNED: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with a high mortality rate and limited treatment efficacy. Nintedanib, a tyrosine kinase inhibitor, is clinically used to treat pulmonary fibrosis. At present, only nintedanib is on the market for the treatment of pulmonary fibrosis.
Pazopanib is a drug for the treatment of renal cell carcinoma and advanced soft tissue sarcoma.
UNASSIGNED: In this study, we explored whether
pazopanib can attenuate bleomycin (BLM)-induced pulmonary fibrosis and explored its antifibrotic mechanism. In vivo and in vitro investigations were carried out to investigate the efficacy and mechanism of action of pazopanib in pulmonary fibrosis.
UNASSIGNED: In vivo experiments showed that
pazopanib can alleviate pulmonary fibrosis caused by BLM, reduce the degree of collagen deposition and improve lung function. In vitro experiments showed that
pazopanib suppressed transforming growth factor-β1 (TGF-β1)-induced myofibroblast activation and promoted apoptosis and autophagy in myofibroblasts. Further mechanistic studies demonstrated that pazopanib inhibited the TGF-β1/Smad and non-Smad signaling pathways during fibroblast activation.
UNASSIGNED: In conclusion, pazopanib attenuated BLM-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.
Pazopanib inhibits myofibroblast activation, migration, autophagy, apoptosis, and extracellular matrix (ECM) buildup by downregulating the TGF-β1/Smad signal route and the TGF-β1/non-Smad signal pathway. It has the same target as nintedanib and is a tyrosine kinase inhibitor.