Targeted blockade of JAK/STAT3 signaling inhibits proliferation, migration and collagen production as well as inducing the apoptosis of hepatic stellate cells
Targeted blockade of JAK/STAT3 signaling inhibits proliferation, migration and collagen production as well as inducing the apoptosis of hepatic stellate cells
复制标题
靶向阻断 JAK/STAT3 信号传导抑制增殖、迁移和胶原蛋白生成并诱导肝星状细胞凋亡
DOI：
10.3892/ijmm.2016.2692
复制
发表时间：
2016-09-01
影响因子：
5.4
通讯作者：
Wei, Wei
中科院分区：
文献类型：
--
作者：
Gu, Yuan-Jing;Sun, Wu-Yi;Wei, Wei
Protein tyrosine kinases belonging to the Janus kinase (JAK) family are associated with many cytokine receptors, which, on ligand binding, regulate important cellular functions such as proliferation, apoptosis and differentiation. The protective effects of JAK inhibitors on fibrotic diseases such as myelofibrosis and bone marrow fibrosis have been demonstrated in previous studies. The JAK inhibitor SHR0302 is a synthetic molecule that potently inhibits all members of the JAK family, particularly JAK1. However, its effect on hepatic fibrosis has not been investigated to date, to the best of our knowledge. In the present study, the effects of SHR0302 on the activation, proliferation, migration and apoptosis of hepatic stellate cells (HSCs) as well as HSC collagen production were investigated. Our data demonstrated that treatment with SHR0302 (10(-9)-10(-5) mol/l) exerted an inhibitory effect on the activation, proliferation and migration of HSCs. In addition, the expression of collagen I and collagen III were significantly decreased following treatment with SHR0302. Furthermore, SHR0302 induced the apoptosis of HSCs, which was demonstrated by Annexin V/PI staining. SHR0302 significantly increased the activation of caspase-3 and Bax in HSCs whereas it decreased the expression of Bcl-2. SHR0302 also inhibited the activation of Akt signaling pathway. The pharmacological inhibition of the JAK1/signal transducer and activator of transcription (STAT)3 pathway led to the disruption of functions essential for HSC growth. Taken together, these findings provide evidence that SHR0302 may have the potential to alleviate hepatic fibrosis by targeting HSC functions.
