Decrease of lactogenic hormones induce epithelial-mesenchymal transition via TGFβ1 and arachidonic acid during...

Area of Science:

• Reproductive biology
• Cellular and molecular biology
• Biochemistry

Background:

• Mammary gland involution involves tissue remodeling and milk production cessation.
• Epithelial mesenchymal transition (EMT) is crucial for mammary gland involution.
• Transforming growth factor β (TGFβ) is a known inducer of EMT during involution.

Purpose of the Study:

• To elucidate the complete mechanism of EMT during mammary gland involution.
• To identify novel players involved in TGFβ-induced EMT.
• To investigate the role of arachidonic acid in mammary gland involution and EMT.

Main Methods:

• Gene expression analysis (CDH1, VIM, TWIST1, TGFB1, PLCG2) during involution.
• In vitro epithelial cell culture experiments.
• Hormone depletion and treatment with arachidonic acid and TGFβ1.
• Inhibition of arachidonic acid synthesis.

Main Results:

• Involution decreased epithelial marker CDH1 and increased mesenchymal markers VIM and TWIST1, along with TGFB1 and PLCG2.
• Arachidonic acid treatment increased mesenchymal markers but not CDH1; TGFβ1 decreased CDH1 and increased mesenchymal markers.
• TGFβ1 induced PLCG2 expression, while arachidonic acid did not induce TGFB1. Arachidonic acid accelerated TGFβ1-induced EMT markers, and its synthesis inhibition partially blocked TGFβ1 effects.

Conclusions:

• Transforming growth factor β (TGFβ1) stimulates arachidonic acid synthesis during mammary gland involution.
• Arachidonic acid acts synergistically with TGFβ1 to promote EMT.
• This study identifies arachidonic acid as a novel factor in mammary gland involution and EMT.