Mo Won Min, Kwon Yang Woo, Jang Il Ho, Choi Eun Jung, Kwon Sang Mo, Kim Jae Ho
Department of Physiology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Department of Oral Biochemistry and Molecular Biology, Pusan National University School of Dentistry, Yangsan 50612, Republic of Korea.
Biomol Ther (Seoul). 2017 Jul 1;25(4):354-361. doi: 10.4062/biomolther.2016.263.
Transcriptional co-activator with a PDZ-binding motif (TAZ) is an important factor in lysophosphatidic acid (LPA)-induced promotion of migration and proliferation of human mesenchymal stem cells (MSCs). The expression of TAZ significantly increased at 6 h after LPA treatment, and TAZ knockdown inhibited the LPA-induced migration and proliferation of MSCs. In addition, embryonic fibroblasts from TAZ knockout mice exhibited the reduction in LPA-induced migration and proliferation. The LPA1 receptor inhibitor Ki16425 blocked LPA responses in MSCs. Although TAZ knockdown or knockout did not reduce LPA-induced phosphorylation of ERK and AKT, the MEK inhibitor U0126 or the ROCK inhibitor Y27632 blocked LPA-induced TAZ expression along with the reduction in the proliferation and migration of MSCs. Our data suggest that TAZ is an important mediator of LPA signaling in MSCs in the downstream of MEK and ROCK signaling.
含PDZ结合基序的转录共激活因子（TAZ）是溶血磷脂酸（LPA）诱导人间充质干细胞（MSC）迁移和增殖的重要因子。LPA处理后6小时，TAZ的表达显著增加，TAZ基因敲低抑制了LPA诱导的MSC迁移和增殖。此外，TAZ基因敲除小鼠的胚胎成纤维细胞表现出LPA诱导的迁移和增殖减少。LPA1受体抑制剂Ki16425阻断了MSC中的LPA反应。虽然TAZ基因敲低或敲除并未降低LPA诱导的ERK和AKT磷酸化，但MEK抑制剂U0126或ROCK抑制剂Y27632阻断了LPA诱导的TAZ表达以及MSC增殖和迁移的减少。我们的数据表明，TAZ是MEK和ROCK信号下游MSC中LPA信号的重要介质。
