半乳糖凝集素-3 (Galectin-3)在放射性肺纤维化发生发展中的作用及机制

As a multifunctional biomarker, galectin-3 palys an important role in detecting tissue fibrosis and inflammatory process. Numerous studies have been elucidating the role of galectin-3 in the devolopment of organ fibrosis. However, the effect of galectin-3 and its targeted therapy in pulmonary fibrosis with radiation therapy for thoracic neoplasm has been given less attention.Our preliminary studies showed that galectin-3 expression was increased in the radiation induced pulmonary fibrosis (RPF)model.Moreover,our previous studies have also confirmed that genetic disruption of galectin-3 and pharmacological inhibition of galectin-3 attenuated the progression of cardiac remodeling in murine and rat models of heart failure. Inhibition of galectin-3 largely preserved systolic and diastolic function via the inhibition of myocardial fibrosis and decreased collagen production、 processing and cross-linking. Therefore,our hypothesis is that galectin-3 will exert an important role in the pulmonary fibrogenesis and collagen synthesis and deposition process by modulating the activity of myofibroblast in the development of RPF. Herein, in the present study, we will firstly employ galectin-3 knock out and C57BL/6 WT mice , which will be subjected to whole thoracic irradiation to provoke pulmonary fibrosis. Secondly, the galecitn-3 inhibitor will be administered to the irradiated C57BL/6 mice. By taking advantage of micro-PET CT、RT-PCR、Western-blot, we further analyze the effect of galectin-3 inhibition on RPF . We believe that the oncoming results of this study will provide not only a new and more advanced mechanisms in fibrogenesis process, but also a novel therapeutic means for RPF.

半乳糖凝集素-3(Gal-3)作为一种新型的多功能生物标记物参与调控炎症和组织纤维化的病理进程。迄今对Gal-3在放射性肺纤维化（RPF）中的作用和机制仍知之甚少。我们在预实验中发现Gal-3在RPF中表达升高，且前期工作亦证实了Gal-3可通过调控心肌成纤维细胞活性及胶原蛋白的合成、分泌与沉积来影响心肌组织重塑的病理进程。因此，我们推测Gal-3可通过对肺肌成纤维细胞活性的调控来影响肺组织纤维增生,从而导致RPF的发展。我们将通过RPF细胞模型、Gal-3基因敲除小鼠和Gal-3抑制剂处理的RPF模型，采用分子影像、 RT-PCR、Western-blot、免疫组化等手段，从分子、细胞、组织以及整体动物水平等多方面探讨Gal-3在RPF中的重要作用，明确Gal-3在RPF中的作用及机制，本研究将从Gal-3这个新视点揭示RPF的发生机制，并为RPF的进一步防治提供新的思路。