Mechanisms and research progress of progranulin in organ fibrotic diseases

Fibrotic diseases are the common pathological outcome of various chronic tissue injuries, characterized by excessive deposition of extracellular matrix (ECM)and organ dysfunction. The pathogenesis is complex, and effective treatment strategies are lacking. Progranulin (PGRN), a multifunctional secretory glycoprotein, exhibits a complex and organ-specific bidirectional regulatory effect in the process of fibrosis. This review systematically elaborates on the role of PGRN in various fibrotic 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 activation, and collagen deposition. PGRN shows a pro-fibrotic effect, 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 provide new ideas for overcoming the therapeutic bottleneck in fibrotic diseases.