妊娠期糖尿病（gestational diabetes mellitus, GDM）是在懷孕期間被診斷出糖尿病會造成死胎、先天性畸形、巨嬰症、胎盤發炎與早產。前胸腺素（prothymosin α, ProT）是一種高度酸性核蛋白參與在多種細胞功能中，例如：細胞週期、細胞增生還有免疫調節的作用。我們實驗室先前的研究顯示ProT會透過抑制胰島素訊息路徑導致胰島素抗性的發展。在本研究中，我們想探討ProT在妊娠期糖尿病中扮演的角色。我們先收取人類胎盤與血漿利用反轉錄酶聚合連鎖反應與西方墨點法分析。發現ProT mRNA和蛋白質在妊娠期糖尿病患者表現量高於一般健康孕婦。利用第一型膠原蛋白（collagen type I, Col I）來檢測結締組織的表現量，妊娠期糖尿病患者胎盤Col I表現量高於一般懷孕婦女。接下來在細胞實驗，我們過量與剔除ProT在3ASubE人類滋養層細胞中，發現ProT可以調控Col I。我們在在用葡萄糖和甲基乙二醛（methylglyoxal）處理的人類滋養層細胞發現可以增強ProT表現量。在用葡萄糖和甲基乙二醛處理的滋養細胞中Col I和ProT表達有升高，但是我們使用ROS抑制劑（N-acetyl-L-cysteine）發現Col I表達會降低。在動物實驗中，我們收集C57BL/6小鼠不同天數的胎盤。我們結果知道ProT會在懷孕週期第13與15天高表現。我們利用鏈脲佐菌素（streptozocin）建立了妊娠期糖尿病小鼠模式。發現妊娠期小鼠ProT、血糖、Col I與胎盤重量都高於一般野生型懷孕小鼠。而血漿中胰島素低於一般野生型小鼠。我們也過量表現ProT在人類滋養層細胞中發現會增強NFB活化與使用NFB抑制劑處理後會降低Col I表現量。我們也發現過量表現ProT會增強凋亡作用（apoptosis）caspase-3的表現。總結我們的結果，顯示ProT可以增加胎盤結締組織進而幫助妊娠期糖尿病胎盤結締組織的病態發展。ProT可能可以當作標靶治療妊娠期糖尿病的一種方向。

Gestational diabetes mellitus (GDM) is a diabetes diagnosed during pregnancy that causes stillborn, congenital malformations, giant baby syndrome, placenta inflammation, and premature birth. Prothymosin α (ProT) is a highly acidic protein with a wide distribution. ProT is involved in diverse intracellular and extracellular functions, such as cell proliferation, apoptosis, oxidative stress, and immunomodulation. We have shown that ProT contributes to the pathogenesis of insulin resistance through inhibiting insulin signaling. In this study, we investigated the potential role of ProT in GDM. We collected human placenta tissue and plasma for quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and western blotting. The expressions of ProT mRNA and protein were higher in GDM patients than in healthy pregnant women. Connective tissue of the placenta examined by type I collagen (collagen I) expression was more serious in GDM patients compared with their normal pregnant women. Next, we overexpressed and knocked down ProT expression in the 3AsubE trophoblast cell line and found that ProT could enhance collagen I expression. Treatment with glucose and methylglyoxal enhanced ProT and collagen I expression in trophoblasts, which could be abrogated by addition of the ROS inhibitor N-acetyl-L-cysteine (NAC). In animal models, we collected the placenta tissue of C57BL/6 mice at different phases of pregnancy. Our results revealed that ProT was overexpressed at 13 and 15 days of the pregnancy cycle. We used streptozotocin (STZ) to induce diabetes in mice as the GDM animal model. The GDM mice had higher levels of ProT, fasting bloodglucose, collagen I, and placenta weight than the normal mice. Furthermore, levels of plasma insulin were lower in the GDM mice than normal mice. Overexpression of ProT in 3ASubE placenta trophoblast cells enhanced NFB activation. Moreover, treatment with an NFkB inhibitor downregulated collagen I expression. We also observed that overexpression of ProT enhanced the expression of the apoptosis marker caspase-3. Taken together, our results demonstrate that ProT can increase the placenta connective tissue and thereby contribute to the pathogenesis of placenta connective tissue in GDM. Our data also suggest that ProT may be a therapeutic target for GDM.

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