Journal
ISCIENCE
Volume 23, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2020.100961
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Funding
- National Research Foundation of Korea (NRF) - Korean Government, Ministry of Science and ICT (MSIT) [NRF-2018R1A5A2025079]
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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 alpha 5, which abolished the phosphorylation of integrin beta 3. We found that Serpina3c inhibits a serine protease that regulates integrin alpha 5 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 GSK3 beta. Altogether, our results indicate that Serpina3c secreted from differentiating adipocytes inhibits serine proteases tomodulate integrin/IGF-1-mediated ERK and AKT signaling and thus is a critical factor contributing to adipogenesis.
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