J Anim Sci. 2017 Dec;95(12):5278-5289. doi: 10.2527/jas2017.1885.
Cell-cell interactions between epithelial and stromal cells are predominant in the mammary gland, and various stromal cell-derived factors can elicit mitogenic responses in adjacent epithelial cells. Adiponectin is a hormone secreted mainly by adipocytes that mediates stromal-epithelial interactions in a number of tissues. Adiponectin receptors are expressed by bovine mammary epithelial cells, but the regulatory effects of adiponectin on the development and function of the mammary gland remain unclear. We therefore sought to investigate the effects of adiponectin on bovine mammary epithelial (MAC-T) cells and the regulatory mechanisms that underlie these adiponectin-induced actions. Our results revealed an increase in MAC-T cell proliferation and cell cycle progression in response to adiponectin. The expression of nuclear proliferating cell nuclear antigen (PCNA) and cyclin D1 was induced in MAC-T cells, and intracellular signaling molecules such as serine/threonine protein kinase (AKT), 70 kDa ribosomal S6 kinase (P70S6K), ribosomal protein S6 (S6), extracellular signal-regulated kinases 1 and 2 (ERK1/2), 90 kDa ribosomal S6 kinase (P90S6K), and cyclin D1 were activated in a dose-dependent manner. The abundance of adiponectin-induced signaling proteins was suppressed following inhibition of AKT or ERK1/2 mitogen-activated protein kinase (MAPK) signaling. In addition, inhibition of AKT or ERK1/2 signaling significantly reduced adiponectin-stimulated MAC-T cell proliferation. Furthermore, adiponectin reduced tunicamycin-induced expression and activation of endoplasmic reticulum stress-related proteins in MAC-T cells and attenuated the repressive effect of tunicamycin on proliferation of MAC-T cells. Collectively, these results suggest that adiponectin-mediated signaling may affect the development and function of the mammary gland in dairy cows by increasing mammary epithelial cell numbers. These findings may result in important implications for improving our fundamental understanding of lactation physiology in livestock species.
上皮细胞和基质细胞之间的细胞-细胞相互作用在乳腺中占主导地位，各种基质细胞衍生的因子可以刺激相邻上皮细胞的有丝分裂反应。脂联素是一种主要由脂肪细胞分泌的激素，它介导许多组织中的基质-上皮相互作用。脂联素受体在牛乳腺上皮细胞中表达，但脂联素对乳腺发育和功能的调节作用尚不清楚。因此，我们试图研究脂联素对牛乳腺上皮（MAC-T）细胞的影响及其调节机制。我们的结果显示，脂联素能促进 MAC-T 细胞增殖和细胞周期进程。MAC-T 细胞中核增殖细胞核抗原（PCNA）和细胞周期蛋白 D1 的表达增加，丝氨酸/苏氨酸蛋白激酶（AKT）、70 kDa 核糖体 S6 激酶（P70S6K）、核糖体蛋白 S6（S6）、细胞外信号调节激酶 1 和 2（ERK1/2）、90 kDa 核糖体 S6 激酶（P90S6K）和细胞周期蛋白 D1 等细胞内信号分子也呈剂量依赖性激活。AKT 或 ERK1/2 丝裂原活化蛋白激酶（MAPK）信号通路被抑制后，脂联素诱导的信号蛋白丰度降低。此外，抑制 AKT 或 ERK1/2 信号通路显著降低了脂联素刺激的 MAC-T 细胞增殖。此外，脂联素降低了 tunicamycin 诱导的 MAC-T 细胞内质网应激相关蛋白的表达和激活，并减轻了 tunicamycin 对 MAC-T 细胞增殖的抑制作用。总之，这些结果表明，脂联素介导的信号通路可能通过增加乳腺上皮细胞数量来影响奶牛乳腺的发育和功能。这些发现可能对提高我们对家畜泌乳生理学的基本理解具有重要意义。
