The Signaling Mechanism of TGF-β 1 Induced Bovine Mammary Epithelial Cell Apoptosis

• Published in: Asian-australasian journal of animal sciences Vol. 25; no. 3; pp. 304 - 310
• Main Authors: Di, He-Shuang, Wang, Li-Gang, Wang, Gen-Lin, Zhou, Lei, Yang, Yuan-Yuan
• Format: Journal Article
• Language: Korean
• Published: 2012
• Subjects: Mammary Epithelial Cell; TGF- ${\beta}_1; [ $Ca^{2+}$]i; p-Smad2/3; ALK-5
• ISSN: 1011-2367; 1976-5517

The present study showed that Transforming growth factor beta 1 (TGF-${\beta}_1$) can induce apoptosis of bovine mammary epithelial cells. This apoptosis was also observed with phosphorylation of Smad2/3 within 0.5-2 h. Afterwards the signal transferred into the nucleus. Moreover, intracellular free $Ca^{2+}$ concentration was significantly elevated as well as Caspase-3 activated and DNA lysised, thereby inducing the programmed cell death. This signaling pathway of TGF-${\beta}_1$ was blocked by SB-431542 ($10^{-2}{\mu}M$) via inhibiting ALK-5 kinase activity, which thus reversed the anti-proliferation and apoptosis effect of TGF-${\beta}_1$ in mammary epithelial cells. These results indicated that TGF-${\beta}_1$ induced apoptosis of bovine mammary epithelial cells through the ALK-5-Smad2/3 pathway, which plays an important role in inhibiting survival of mammary epithelial cells. Moreover, intracellular $Ca^{2+}$ also played a critical role in TGF-${\beta}_1$-induced cell apoptosis.