Down-regulation of focal adhesion kinase by short hairpin RNA increased apoptosis of rat hepatic stellate cells

作者：An, Junyan; Zheng, Libo; Xie, Shurui; Dun, Zhina; Hao, Lisen; Yao, Dongmei; Shih, David Q.; Zhang, Xiaolan^*

来源：Acta Pathologica, Microbiologica et Immunologica Scandinavica, 2011, 119(6): 319-329.

DOI：10.1111/j.1600-0463.2011.02720.x

• Apoptosis
• focal adhesion kinase
• hepatic stellate cells
• proliferation
• RNA interference

Focal adhesion kinase (FAK) plays an essential role in the activation of hepatic stellate cells (HSC). The role of FAK on proliferation and apoptosis of fibronectin (FN)-stimulated HSC was investigated using short hairpin RNA (shRNA)-mediated gene silencing technology. FAK shRNA decreased the expressions of FAK, p-FAK (Tyr397), ERK1, and p-ERK1. FAK gene silencing also inhibited HSC proliferation by 11.08% at 12-h, 15.12% at 24-h, and 28.62% at 48-h post-transfection. Flow cytometric analysis (FACS) revealed that the apoptotic rate at 24 h was increased in the FAK shRNA plasmid group compared with the HK group (8.29 +/- 0.79% vs 2.70 +/- 0.31%, p < 0.01). TUNEL also confirmed the increase in the rate of apoptosis (19.00 +/- 0.92% vs 7.63 +/- 0.70%, p < 0.01), and studies showed that the caspase-3 expression was increased while the ratio of Bcl-2 to Bax was decreased. Together, these data show that FAK regulates HSC proliferation and induces the apoptosis of HSC via the caspase-3 and Bcl-2/Bax pathway.

• 出版日期2011-6
• 单位河北医科大学