脏器纤维化疾病与原颗粒蛋白的作用机制及研究进展OA

Fibrotic diseases are the common pathological out-come of various chronic tissue injuries,characterized by exces-sive deposition of extracellular matrix(ECM)and organ dys-function.The pathogenesis is complex,and effective treatment strategies are lacking.Progranulin(PGRN),a multifunctional secretory glycoprotein,exhibits a complex and organ-specific bi-directional regulatory effect in the process of fibrosis.This re-view systematically elaborates on the role of PGRN in various fi-brotic diseases and the research progress.In the progression of pulmonary fibrosis and liver fibrosis,PGRN primarily exerts an antifibrotic effect by inhibiting key signaling pathways such as TGF-β/Smad,MAPK(ERK/JNK/p38),and NF-κB,reducing the release of inflammatory factors,inhibiting fibroblast activa-tion,and collagen deposition.PGRN shows a pro-fibrotic ef-fect,possibly promoting fibrosis through the activation of the TGF-β/Smad pathway.Despite the significant potential of PGRN as an antifibrotic therapeutic target,the differences in its effects on fibrosis in different organs and the complex regulatory networks require further clarification.Future research should focus on elucidating the tissue-specific mechanisms of PGRN,developing targeted therapies based on PGRN or its derivatives,and validating its value as a biomarker in clinical diagnosis,prognosis evaluation,and treatment monitoring.This would pro-vide new ideas for overcoming the therapeutic bottleneck in fi-brotic diseases.