Tetramethylpyrazine improves the structure and function of mitochondrial-associated endoplasmic reticulum membrane and liver fibrosis

INTRODUCTION: Morphological and functional abnormalities of mitochondrial-associated endoplasmic reticulum (ER) membrane (MAM) have emerged as a key mediator of organelle dysfunction during liver fibrosis. Tetramethylpyrazine (TMP) was investigated as a potential therapy for liver fibrosis with an unclear mechanism. OBJECTIVES: Considering the changes of MAM quantity and gap distance during liver fibrosis, we aimed to investigate the underlying mechanisms and their potential as therapeutic targets for TMP in inhibiting liver fibrosis. METHODS: -induced fibrosis models both in vivo and in vitro and examined key signaling in patients with fibrosis. RESULTS: overload in mitochondria. Notably, findings in fibrosis patients and hepatic MFN2 knockdown mice further underscored the crucial role of MFN2-mediated normalization of MAM in improving liver fibrosis and the therapeutic effects of TMP. CONCLUSION: Here, we highlight the therapeutic potential of TMP in liver fibrosis by elucidating its role in repairing hepatic MAM.