Metabolism and Targeted Therapy of Fibrosis in Chronic Pancreatitis: A Review.

Abstract

Chronic pancreatitis (CP) is a progressive condition characterized by persistent pancreatic inflammation, tissue destruction, and fibrosis. Recent studies have highlighted the crucial role of metabolic processes in the pathogenesis of pancreatic fibrosis, particularly the metabolic reprogramming of pancreatic stellate cells (PSCs) and immune cells. Disruptions in glucose, lipid, and amino acid metabolism have been shown to play a key role in the progression of CP fibrosis, exacerbating disease severity. Activated PSCs exhibit enhanced glycolysis and lipid metabolism, which promote excessive extracellular matrix (ECM) production and tissue remodeling. Simultaneously, immune cells such as macrophages and T cells undergo metabolic reprogramming, further intensifying inflammation and fibrosis. This review discusses the role of metabolic reprogramming in pancreatic fibrosis and proposes potential therapeutic strategies targeting metabolic pathways, including glycolysis inhibitors, lipid metabolism modulators, and amino acid metabolism regulators. These strategies offer promising prospects for mitigating the progression of CP fibrosis and provide new therapeutic avenues for clinical applications.