Choi Yoonjeong, Choi Hyeonjin, Yoon Bo Kyung, Lee Hyemin, Seok Jo Woon, Kim Hyo Jung, Kim Jae-Woo
Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul 03722, South Korea.
Department of Biochemistry and Molecular Biology, Chronic Intractable Disease for Systems Medicine Research Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
iScience. 2020 Mar 27;23(3):100961. doi: 10.1016/j.isci.2020.100961. Epub 2020 Mar 4.
Preadipocyte differentiation can be induced upon a hormonal treatment, and various factors secreted by the cells may contribute to adipogenesis. In this study, RNA-seq revealed Serpina3c as a critical factor regulating the signaling network during adipogenesis. Serpina3c is a secretory protein and is highly expressed in fat tissues. Knockdown of Serpina3c decreased adipogenesis by attenuating the mitotic clonal expansion of 3T3-L1 cells. These cells exhibited decreases in integrin α5, which abolished the phosphorylation of integrin β3. We found that Serpina3c inhibits a serine protease that regulates integrin α5 degradation. Knockdown of Serpina3c disrupted integrin-mediated insulin growth factor 1 (IGF-1) signaling and ERK activation. Serpina3c-mediated regulation of integrin-IGF-1 signaling is also associated with AKT activation, which affects the nuclear translocation of GSK3β. Altogether, our results indicate that Serpina3c secreted from differentiating adipocytes inhibits serine proteases to modulate integrin/IGF-1-mediated ERK and AKT signaling and thus is a critical factor contributing to adipogenesis.
前脂肪细胞分化可通过激素处理诱导，细胞分泌的各种因子可能有助于脂肪生成。在本研究中，RNA测序显示Serpina3c是脂肪生成过程中调节信号网络的关键因子。Serpina3c是一种分泌蛋白，在脂肪组织中高度表达。敲低Serpina3c可通过减弱3T3-L1细胞的有丝分裂克隆扩增来减少脂肪生成。这些细胞中整合素α5减少，这消除了整合素β3的磷酸化。我们发现Serpina3c抑制一种调节整合素α5降解的丝氨酸蛋白酶。敲低Serpina3c会破坏整合素介导的胰岛素生长因子1（IGF-1）信号传导和ERK激活。Serpina3c介导的整合素-IGF-1信号调节也与AKT激活有关，AKT激活会影响GSK3β的核转位。总之，我们的结果表明，分化的脂肪细胞分泌的Serpina3c抑制丝氨酸蛋白酶，以调节整合素/IGF-1介导的ERK和AKT信号传导，因此是促进脂肪生成的关键因子。
