TGF-β1/CTGF信号通路介导胰腺星形细胞活化在慢性胰腺炎纤维化中的分子机制研究

Chronic pancreatitis(CP) is aclinical refractory disease with resistance to cure, and the most typicalhistopathological feature of CP is pancreatic fibrosis, which closely relatedto the activation of pancreatic stellate cells(PSCs). Transforming growth factor-betal(TGF-β1) plays animportant role in PSCs activation, and it cooperates with its downstreammediator connective tissue growth factor(CTGF/CCN2）inchronic pancreatic fibrosis. Until now, there has been no study demonstratingthe abstract mechanism of TGF-β1/CTGF signal pathway inpancreatic fibrosis. Our preliminary study confirmed that the expression levelsof TGF-β1 and CTGF increased in both the serum and pancreatic tissueof CP. In our study, we use ELISA, RT-PCR and siRNA methods to confirm thatTGF-β1/CTGF signal pathway participates in the pancreatic fibrosisfrom cellular, animal and organizations levels, and the regulation of relationsbetween TGF-β1 and CTGF signal pathway wereevaluated through the intervention of intermediate factor of TGF-β1 and CTGF, eventually toclarify the role of TGF-β1/CTGF signal pathway in the fibroticmechanism of CP. In conclution, we aim to find out a new way for the treatmentof CP.

慢性胰腺炎（CP）是一种临床难治性疾病，主要病理特征是胰腺纤维化，其与胰腺星形细胞（PSCs）的活化密切相关。转化生长因子-β1（TGF-β1）在PSCs活化中起着关键的作用，其协同下游产物结缔组织生长因子（CTGF/CCN2）共同参与胰腺纤维化形成。但尚无研究探讨TGF-β1/CTGF信号通路在胰腺纤维化中的具体作用机制。前期研究我们发现CP患者血清及胰腺组织中TGF-β1和CTGF的表达较正常人群升高。本研究拟采用RT-PCR、免疫组化和siRNA干扰等技术，从细胞、动物模型、人体组织三个水平分别评价TGF-β1/CTGF信号通路间的调控关系，通过干预TGF-β1、CTGF信号通路的中间环节，阐明TGF-β1/CTGF信号通路在胰腺纤维化中的作用机制，为CP治疗提供新的靶点和手段。