Anand Vijay, Jaswal Shalini, Singh Surender, Kumar Sudarshan, Jena Manoj Kumar, Verma Arvind Kumar, Yadav Munna Lal, Janjanam Jagadeesh, Lotfan Masoud, Malakar Dhruba, Dang Ajay Kumar, Mohanty Tushar Kumar, Kaushik Jai Kumar, Mohanty Ashok Kumar
Animal Biotechnology Centre, National Dairy Research Institute (NDRI), Karnal, 132001, India.
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Apoptosis. 2016 Feb;21(2):209-24. doi: 10.1007/s10495-015-1196-z.
MGP-40 is a chitinase-like protein which is over expressed during mammary gland involution. However, its physiological function in the mammary gland is poorly understood. In the present investigation, we have reported the functional significance of buffalo specific MGP-40 in the mammary gland by using an in vitro model of the buffalo mammary epithelial cell (BuMEC) line. MGP-40 was highly up regulated in BuMECs in serum starved condition as well as after treatment with prolactin suggesting its role in the stress response. Subsequently, to study the effect of MGP-40 on BuMECs, the cells were transfected with a mammalian expression construct of pCI neo harboring MGP-40 gene. It was observed that over expression of MGP-40 enhanced proliferation of BuMECs and protected the cells from apoptosis under serum free condition. In contrast, MGP-40 attenuated the mitogenic effect of insulin in BuMECs. Besides, over expression of the MGP-40 reduced dome formation, acinar polarization and casein synthesis in BuMECs in the presence of lactogenic hormones, it also induced Stat3 phosphorylation and epithelial to mesenchymal transition (EMT) -like features. Together, our data suggest that MGP-40 is involved in protection of BuMECs under stress conditions, inhibits cellular differentiation and induces EMT-like features. A schematic diagram depicting possible association of MGP-40 in various molecular pathways has been presented.
MGP - 40是一种几丁质酶样蛋白,在乳腺退化过程中过度表达。然而,其在乳腺中的生理功能尚不清楚。在本研究中,我们通过使用水牛乳腺上皮细胞(BuMEC)系的体外模型,报道了水牛特异性MGP - 40在乳腺中的功能意义。在血清饥饿条件下以及用催乳素处理后,BuMECs中MGP - 40高度上调,表明其在应激反应中的作用。随后,为了研究MGP - 40对BuMECs的影响,用携带MGP - 40基因的pCI neo哺乳动物表达构建体转染细胞。观察到MGP - 40的过表达增强了BuMECs的增殖,并在无血清条件下保护细胞免于凋亡。相反,MGP - 40减弱了胰岛素在BuMECs中的促有丝分裂作用。此外,在存在泌乳激素的情况下,MGP - 40的过表达减少了BuMECs中的穹顶形成、腺泡极化和酪蛋白合成,还诱导了Stat3磷酸化和上皮 - 间质转化(EMT)样特征。总之,我们的数据表明MGP - 40参与应激条件下对BuMECs的保护,抑制细胞分化并诱导EMT样特征。本文呈现了一个描述MGP - 40在各种分子途径中可能关联的示意图。