李宜儒Yi-Ju Lee郭珈諭Jia-Yu Kuo生化微生物免疫研究所2026-10-299999-12-312019https://handle.ncl.edu.tw/11296/bqyqnbhttps://scholars.csmu.edu.tw/handle/123456789/36410乳腺的最終功能是合成乳汁以滋養新生兒。在懷孕期間，乳腺細胞大量增生並從現有的管道發芽形成腺泡。然後豐富的腺泡細胞獲得在哺乳期間合成乳汁的能力。這種特定的形態發生和功能分化受各種激素和生長因子的控制。新興的參與者是T輔助（Th）2細胞因子。使用初代小鼠乳腺上皮細胞的3D培養，我們已經顯示介白素（IL）-4和IL-13通過STAT6刺激細胞增生。在這項研究中，我們進一步揭示IL-4和IL-13增加胰島素受體受質-1（IRS-1）的表達和酪氨酸磷酸化，這是參與IL-4 / IL-13信號傳導的另一個關鍵分子。STAT6可以引導IRS-1，因為抑制了STAT6活性會降低了IRS-1表達和酪氨酸磷酸化。用胰島素和IL-4 / IL-13共處理細胞增強了催乳素和STAT5酪氨酸磷酸化的水平，表明響應Th2細胞因子和胰島素的IRS-1的上調可能賦予乳腺細胞內源性催乳素產生。總之，我們的結果表明IL-4 / IL-13與胰島素信號傳導之間存在交流(crosstalk)，這可能有助於乳腺發育。The ultimate function of mammary glands is to synthesize milk to nourish the newborn. During pregnancy, mammary cells proliferate substantially and bud from the existing ducts to form alveoli. Abundant alveolar cells then acquire the ability to synthesize milk during lactation. This particular morphogenesis and functional differentiation are controlled by various hormones and growth factors. The emerging players are T helper (Th)2 cytokines. Using 3D cultures of primary mouse mammary epithelial cells, we have shown that interleukin (IL)-4 and IL-13 stimulate cell proliferation via STAT6. In this study, we further revealed that IL-4 and IL-13 augment expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), another crucial molecule involved in IL4/IL-13 signaling. This was mediated by STAT6 as inhibition of STAT6 activity reduced IRS-1 expression and tyrosine phosphorylation. Cotreatment of cells with insulin and IL-4/IL-13 enhanced levels of prolactin and STAT5 tyrosine phosphorylation, suggesting that upregulation of IRS-1 in response to Th2 cytokines and insulin might confer endogenous prolactin production in mammary cells. Taken together, our results suggest a crosstalk between IL-4/IL-13 and insulin signaling, which may help mammary gland development.乳腺介白素-4介白素-13胰島素受體受質-1mammary glandIL-4IL-13IRS-1thesis