Tryptophan catabolism is dysregulated in leiomyomas.
Tryptophan catabolism is dysregulated in leiomyomas.
复制标题
色氨酸分解代谢在平滑肌瘤中失调。
DOI：
10.1016/j.fertnstert.2021.05.081
复制
发表时间：
2021-10
影响因子：
6.7
通讯作者：
Khorram O
中科院分区：
文献类型：
--
作者：
Chuang TD;Quintanilla D;Boos D;Khorram O
确定吲哚胺 2,3-双加氧酶 (IDO1) 和色氨酸 2,3-双加氧酶 (TDO2) 在平滑肌瘤中的表达和功能作用。实验研究学术研究实验室接受子宫肌瘤切除术的女性。封锁 IDO1 和 TDO2。 IDO1和TDO2在平滑肌瘤中的表达及其抑制剂对细胞外基质（ECM）的影响。与匹配的子宫肌瘤相比，平滑肌瘤表达显着更高水平的 IDO1 和 TDO2 mRNA（分别为 60.3%，35/58 对；98.3%，57/58 对）和蛋白质（分别为 54%，27/50 对；92%，46/50 对），以及犬神经氨酸（KYN；78.3%，36/46 对），这是子宫肌瘤的标志物。酶活性。与白人和西班牙裔患者相比，非裔美国人 (AA) 肌瘤中 TDO2 mRNA 的表达显着升高，但 IDO1 mRNA 的表达不显着升高。与野生型平滑肌瘤相比，携带 MED12 突变的肌瘤中 TDO2（而非 IDO1）蛋白和 mRNA 水平更丰富。用 TDO2 抑制剂 680C91（而非 IDO1 抑制剂 Epacodostat）治疗 LSMC（平滑肌瘤平滑肌细胞）和 MSMC（子宫肌层平滑肌细胞）球体，可显着抑制细胞增殖以及 I 型胶原 (COL1A1) 和 III 型胶原 (COL3A1) 的表达，且呈剂量依赖性；与 MSMC 球体相比，这些效应在 LSMC 中更为明显。这些结果强调了色氨酸降解途径在平滑肌瘤发病机制中的生理意义以及抗TDO2药物治疗平滑肌瘤的潜在用途。色氨酸分解代谢通过上调两种关键酶 IDO1 和 TDO2 在平滑肌瘤发病机制中发挥作用
To determine the expression and functional roles of indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO2) in leiomyoma. Experimental study Academic research laboratory Women undergoing hysterectomy for leiomyoma. Blockade of IDO1 and TDO2. Expression of IDO1 and TDO2 in leiomyoma and the effects of their inhibitors on extracellular matrix (ECM). Leiomyoma as compared with matched myometrium expressed significantly higher levels of IDO1 and TDO2 mRNA (60.3%, 35/58 pairs; 98.3%, 57/58 pairs, respectively) and protein (54%, 27/50 pairs; 92%, 46/50 pairs, respectively), and kyneurenine (KYN; 78.3%, 36/46 pairs), a marker of enzyme activity. The expression of TDO2 but not IDO1 mRNA was significantly higher in fibroids from African American (AA) as compared with Caucasian and Hispanic patients. TDO2 but not IDO1 protein and mRNA levels were more abundant in fibroids bearing the MED12 mutation as compared with wild type leiomyomas. Treatment of LSMC (leiomyoma smooth muscle cells) and MSMC (myometrial smooth muscle cells) spheroids with the TDO2 inhibitor, 680C91 but not the IDO1 inhibitor, Epacodostat significantly repressed cell proliferation and the expression of collagen type I (COL1A1) and type III (COL3A1) in a dose-dependent manner; these effects were more pronounced in LSMC as compared with MSMC spheroids. These results underscore the physiological significance of tryptophan degradation pathway in the pathogenesis of leiomyomas and the potential utility of anti-TDO2 drugs for treatment of leiomyomas. Tryptophan catabolism plays a role in leiomyoma pathogenesis through upregulation of two key enzymes IDO1 and TDO2
登录
查看更多内容
影响因子：
3.9
作者：
Chuang TD;Panda H;Luo X;Chegini N
通讯作者：
Chegini N
影响因子：
2.9
作者：
Chuang, Tsai-Der;Khorram, Omid
通讯作者：
Khorram, Omid
影响因子：
4.8
作者：
HIROTA, T;HIROTA, K;TANAKA, T
通讯作者：
TANAKA, T
影响因子：
6.7
作者：
Chuang TD;Rehan A;Khorram O
通讯作者：
Khorram O
影响因子：
6.7
作者：
Chuang, Tsai-Der;Khorram, Omid
通讯作者：
Khorram, Omid