The Extracts from Two Antarctic Fish Species, Trematomus newnesi and Trematomus bernacchii, Enhance JEG‐3 Cell Migration and Invasion via MMP9 Activation Through Akt/Protein Phosphatase1/β‐Catenin Pathway

• Published in: Molecular nutrition & food research 2024-08, Vol.68 (15), p.e2400028-n/a
• Main Authors: Khaliq, Sana Abdul, Kim, Jaewon, Kim, Il‐Chan, Kim, Jin‐Hyoung, Yoon, Mee‐Sup
• Format: Article
• Language: English
• Subjects: AKT protein; Animals; Antarctic region; Antarctic Regions; beta Catenin - metabolism; Catenin; Cell activation; Cell adhesion & migration; Cell Line, Tumor; Cell migration; cell movement; Cell Movement - drug effects; collagen; Dephosphorylation; Fish; food research; Gelatinase B; Humans; In vitro methods and tests; Invasive species; JEG‐3 cell; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; Metalloproteinase; metalloproteinases; migration; migratory behavior; Muscles; Natural products; nutrition; Perciformes - metabolism; Phosphoprotein phosphatase; Pregnancy; Protein phosphatase; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Social organization; tandem mass spectrometry; Taurocholic acid; Trematomus bernacchii; Trematomus newnesi; trophoblast; Trophoblasts - drug effects; Trophoblasts - metabolism; Western blotting; Wound healing
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.202400028

Scope This study investigates the impact of extracts derived from Antarctic fish species, Trematomus newnesi and Trematomus bernacchii, on the migration of human placental trophoblast JEG‐3 cells, which is a crucial aspect of successful pregnancy. Methods and results The extracts, obtained from the muscles of these fish, significantly enhance the migration and invasion of JEG‐3 cells in in vitro wound healing, Transwell, and collagen invasion assays. These effects are accompanied by an increase in matrix metalloproteinase (MMP) 9 activity, as demonstrated by zymography. Furthermore, the extracts activated Akt and protein phosphatase 1, resulting in the dephosphorylation of β‐catenin at Ser33/37/Thr41, as confirmed by western blot analysis. Consequently, MMP9 is upregulated, while metallopeptidase inhibitor 1/3 is downregulated, as verified by western blot and qRT‐PCR analyses. Finally, utilizing ultraperformance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) analysis, followed by matching with the Global Natural Product Social Molecular Networking library, the study annotates the compound responsible for the observed migratory activity as taurocholic acid. Importantly, the study confirms that taurocholic acid enhances cell migration in JEG‐3 cells. Conclusion The results of this study emphasize the potential of Antarctic fish extracts in promoting extravillous trophoblast migration and invasion, which are critical for successful pregnancy. Muscle extracts from Trematomus newnesi and Trematomus bernacchii activate Akt, initiating a cascade leading to β‐catenin dephosphorylation at Ser33/37/Thr41. Dephosphorylated β‐catenin translocates to the nucleus, forming a complex that regulates MMP9, TIMP1, and TIMP3 genes. Taurocholic acid is identified as the migratory compound, enhancing MMP activity and promoting cell migration and invasion in JEG‐3 cells.