Sugathan Subi, Lee Sung-Jin, Shiwani Supriya, Singh Naresh Kumar
Department of Animal Biotechnology, College of Animal Life Sciences, Kangwon National University, Chuncheon 24341, Korea.
Department of Veterinary Surgery and Radiology, Faculty of Veterinary and Animal Sciences, Institute of Agricultural Sciences, Banaras Hindu University,Varanasi-221005, Uttar Pradesh, India.
Asian-Australas J Anim Sci. 2020 Feb 1;33(2):349-359. doi: 10.5713/ajas.18.0806. Epub 2019 Apr 15.
Orchastric changes in the mammary glands are vital, especially during the lactaction. 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 transdifferente towards adipocytes in lactation period. We aimed to inhibit the adipocyte transdifferentiation of luminal cells by restraining the PPARγ pathway. 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.Co-culture with myoepithelial cells showed higher adipogenic gene expression in epithelial cells under LA+TZDs treatment. Increase in the expressions of PPARγ, C/EBPα and vimentin in both mRNA as well as protein levels were observed.Whereas,BADGE 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 found to work better than the others. In summary, antagonizing PPARγ pathway in the presence of myoepithelial cells can significantly reduce the adipogenisis in epithelial cells, suggestingtherapeutic inhibition of PPARγ can be considered to counter early involution or excessive adipogenesis in mammary epithelium in animals.
乳腺的卵巢相关变化至关重要，尤其是在哺乳期。分泌上皮细胞与支持性的肌上皮细胞和基质细胞协同作用以分泌乳汁。在哺乳期可见管腔上皮细胞数量增加而脂肪细胞数量减少，而在退化期则相反。然而，如果哺乳期上皮细胞向脂肪细胞转分化，则会发生早期退化。我们旨在通过抑制PPARγ途径来抑制管腔细胞向脂肪细胞的转分化。在单层、混合培养以及与乳腺肌上皮细胞的Transwell板共培养中进行了亚麻酸（LA）和噻唑烷二酮（TZDs）诱导的乳腺上皮细胞脂肪生成实验。与肌上皮细胞共培养显示，在LA+TZDs处理下，上皮细胞中脂肪生成相关基因表达更高。在mRNA和蛋白质水平上均观察到PPARγ、C/EBPα和波形蛋白的表达增加。然而，BADGE处理阻断了LA+TZDs诱导的脂肪生成，因为它未显示出脂肪相关标志物的显著升高。尽管在混合培养和单层条件下都发现了比较结果，但共培养技术被发现比其他技术效果更好。总之，在肌上皮细胞存在的情况下拮抗PPARγ途径可显著降低上皮细胞的脂肪生成，这表明可以考虑通过治疗性抑制PPARγ来对抗动物乳腺上皮的早期退化或过度脂肪生成。
