Jiawei Taohe Chengqi decoction alleviates angiogenesis associated with LECT2/CD209-mediated macrophage reprogramming in hepatic fibrosis.

BACKGROUND: Hepatic fibrosis (HF) is a key pathological process in the progression of chronic liver diseases to cirrhosis and hepatocellular carcinoma (HCC), accompanied by abnormal remodeling of the intrahepatic vascular network. Evidence suggests that hepatocyte cytokine leukocyte cell-derived chemotaxin 2 (LECT2) and macrophage reprogramming exert crucial effects in angiogenesis. Jiawei Taohe Chengqi Decoction (JTCD) can reduce abnormal angiogenesis in HF, but the specific mechanism remains unclear. PURPOSE: To clarify whether JTCD attenuates HF by inhibiting LECT2 to modulate macrophage reprogramming and influence angiogenesis, laying a theoretical and experimental foundation for the clinical application of traditional Chinese medicine (TCM) in HF therapy. METHODS: In vivo experiments utilized a CCl₄-induced mouse HF model, or an adeno-associated virus (AAV) was employed to construct an HF model that overexpresses or knocks down LECT2 to observe the mechanism of JTCD. In vitro treatment of hepatocytes, macrophages, and endothelial cells using siRNA or co-culture methods to validate the molecular mechanism of JTCD. RESULTS: JTCD effectively alleviates CCl₄-induced mouse HF and reduces angiogenesis by inhibiting LECT2. In vitro studies show that JTCD diminishes the regulatory effect of LECT2/CD209-associated macrophage reprogramming and promotes the polarization of macrophages from M1 to M2. Additionally, in vitro tube formation experiments confirmed that JTCD can partially weaken the impact on endothelial cell tube formation through this mechanism. CONCLUSION: The research results demonstrate that JTCD may contribute to reducing the role of M1 macrophages in angiogenesis by inhibiting LECT2/CD209-associated macrophage reprogramming. Additionally, JTCD improves HF in mice through this mechanism.