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Granulosa cells exposed to fibroblast growth factor 8 and 18 reveal early onset of cell growth and survival
Marashi, Fatemeh Amin; Torabi, Ali & Beaudry, Francis
Abstract
Background: Fibroblast growth factors (FGFs) are growth factors that have diverse
biological activities including broad mitogenic and cell survival activities. They function
through the activation of a specific tyrosine kinase receptor that transduces the signal
by activating several intracellular signaling pathways.
Objective: To identify the different signaling pathways involved in the mechanism of
action of FGF8 and FGF18 on ovine granulosa cells using mass spectrometry.
Materials and Methods: Ovine ovarian granulosa cells were harvested from adult
sheep independently at the stage of the estrous cycle and were cultured at a density
of 500,000 viable cells in 1 ml DMEM/F12 medium for five days. The cells were then
treated on day 5 of culture with 10 ng/mL FGF8 and FGF18 for 30 minutes, and total
cell protein was collected for mass spectrometry.
Results: Mass spectrometry showed that both FGF8 and FGF18 significantly induce
simultaneous upregulation of several proteins, including ATF1, STAT3, MAPK1, MAPK3,
MAPK14, PLCG1, PLCG2, PKCA, PIK3CA, RAF1, GAB1, and BAG2 (> 1.5-fold; p < 0.01).
Conclusion: ATF1 and STAT3 are important transcription factors involved in cell growth,
proliferation and survival, and consequently can hamper or rescue the normal ovine
reproductive system function.
Keywords
Fibroblast growth factors; Proteomics; Mass spectrometry; Granulosa cell; Proliferation.
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