NO Suppresses TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Apoptosis in Mouse Hepatocytes

The researchers in the Institute of Biochemistry and Cell Biology reported a study on the regulation of transforming growth factor-β1 (TGF-β1)-induced apoptosis and EMT by nitric oxide.

 

Apoptosis and epithelial-mesenchymal transition (EMT) are critical events involved in lots of biological and pathological processes. The dysregulation of apoptosis and EMT are closely related to some pathological events, such as tumor formation and metastasis, fibrotic diseases of liver and kidney, and abnormal development of embryos. Pan Xinchao et al. published online in Hepatology this month a novel finding on the control of cell apotosis and EMT.

 

TGF-β1 can induce both apoptosis and EMT in mouse hepatocytes. Nitric oxide (NO) is a small highly reactive molecule that is involved in the regulation of many patho-physiological processes and has a protective role in liver. The study showed that NO donor can inhibit TGF-β1-induced apoptosis and EMT. The endogenous NO production through iNOS expression by transfection or induced by cytokines also inhibited TGF-β1-induced apoptosis and EMT, which further confirmed the physiological function of NO. Further investigations showed that NO can inhibit TGF-β1-inuced apoptosis and EMT by decreasing the intracellular ATP levels and the inactivation of signal transducer and the activator of transcription 3 (STAT3) in hepatocytes. This study is of helpful in deepening the understanding on the mechanism of TGF-β1-induced apoptosis and EMT, and has the potential significance for relevant mediacal applications.

 

This work was supported by the Natural Science Foundation of China, the National Basic Research Program of China, and the Shanghai Science Committee.