Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan.
Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan.
J Biosci Bioeng. 2014 May;117(5):624-31. doi: 10.1016/j.jbiosc.2013.10.018. Epub 2013 Dec 9.
Adipogenesis is important to health and is thought occurring in the two stages of mesenchymal stem cell commitment to a preadipocyte fate and terminal differentiation of the preadipocyte. However, the mechanism of adipogenesis is still not clear. In this study, the roles of p38, extracellular regulated protein kinases 1/2 (ERK1/2), focal adhesion kinase (FAK), RhoA/ROCK, and cytoskeleton in both of the two stages of adipogenesis were assayed. Our results showed that the treatments of SB203580 (the inhibitor of p38) and U0126 (the inhibitor of ERK1/2) suppressed the adipogenesis induced by differentiation medium, and the treatments of PF573228 (a specific inhibitor of FAK), Y27632 (a specific inhibitor of RhoA/ROCK) and cytochalasin D (an inhibitor of cytoskeletal organization) promoted the adipogenesis. The treatments of SB203580 and U0126 significantly inhibited the adipogenic differentiation of hMSCs cultured in differentiation medium in the presence of PF573228, Y27632 or cytochalasin D. Moreover, the treatments of PF573228, Y27632 and cytochalasin D promoted p38 and ERK1/2 phosphorylations, and the treatments of U0126 and SB203580 decreased p38 and ERK1/2 phosphorylations, respectively. These results demonstrated that p38 and ERK1/2 played crucial positive roles in adipogenesis, and FAK, RhoA/ROCK and cytoskeleton played negative roles. Furthermore, FAK, RhoA/ROCK and cytoskeleton affected adipogenesis by regulating the activities of p38 and ERK1/2 which interacted with each other in the process of adipogenesis.
脂肪生成对于健康很重要，被认为发生在间充质干细胞向前脂肪细胞命运的定向和前脂肪细胞的终末分化的两个阶段。然而，脂肪生成的机制尚不清楚。在这项研究中，检测了 p38、细胞外调节蛋白激酶 1/2（ERK1/2）、粘着斑激酶（FAK）、RhoA/ROCK 和细胞骨架在前脂肪生成的两个阶段中的作用。我们的结果表明，SB203580（p38 的抑制剂）和 U0126（ERK1/2 的抑制剂）的处理抑制了分化培养基诱导的脂肪生成，PF573228（FAK 的特异性抑制剂）、Y27632（RhoA/ROCK 的特异性抑制剂）和细胞松弛素 D（细胞骨架组织抑制剂）的处理促进了脂肪生成。SB203580 和 U0126 的处理显著抑制了在 PF573228、Y27632 或细胞松弛素 D 存在下培养于分化培养基中的 hMSC 的脂肪生成分化。此外，PF573228、Y27632 和细胞松弛素 D 促进了 p38 和 ERK1/2 的磷酸化，而 U0126 和 SB203580 的处理分别降低了 p38 和 ERK1/2 的磷酸化。这些结果表明 p38 和 ERK1/2 在脂肪生成中发挥了至关重要的正作用，而 FAK、RhoA/ROCK 和细胞骨架则发挥了负作用。此外，FAK、RhoA/ROCK 和细胞骨架通过调节相互作用的 p38 和 ERK1/2 的活性来影响脂肪生成，在脂肪生成过程中 p38 和 ERK1/2 相互作用。
