Transdifferentiation of bovine epithelial cells towards adipocytes in the presence of myoepithelium

초록

Objective: Orchastric changes in the mammary glands are vital, especially during lactation. The secretary epithelial cells together with the supporting myoepithelial and stromal cells function cordially to secrete milk. Increase in the number of luminal epithelial cells and a decrease in adipocytes are visible during lactation, whereas the reverse happens in the involution. However, an early involution occurs if the epithelial cells transdifferentiate towards adipo-cytes during the lactation period. We aimed to inhibit the adipocyte transdifferentiation of luminal cells by restraining the peroxisomal proliferator-activated receptor gamma (PPAR gamma) pathway. Methods: Linolenic acid (LA) and thiazolidinediones (TZDs) induced adipogenesis in mammary epithelial cells were conducted in monolayer, mixed culture as well as in transwell plate co-culture with mammary myoepithelial cells. Results: Co-culture with myoepithelial cells showed higher adipogenic gene expression in epithelial cells under LA+TZDs treatment. Increase in the expressions of PPAR gamma, CCAAT/enhancer-binding protein a and vimentin in both mRNA as well as protein levels were observed. Whereas, bisphenol A diglycidyl ether treatment blocked LA+TZDs induced adipogenesis, as it could not show a significant rise in adipose related markers. Although comparative results were found in both mixed culture and monolayer conditions, co-culture technic was found to work better than the others. Conclusion: Antagonizing PPAR gamma pathway in the presence of myoepithelial cells can significantly reduce the adipogenisis in epithelial cells, suggesting therapeutic inhibition of PPAR gamma can be considered to counter early involution or excessive adipogenesis in mammary epithelium in animals.

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