Ribosome Biogenesis Serves as a Therapeutic Target for Treating Endometriosis and the Associated Complications.
Ribosome Biogenesis Serves as a Therapeutic Target for Treating Endometriosis and the Associated Complications.
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DOI：
10.3390/biomedicines10010185
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发表时间：
2022-01-17
期刊：
影响因子：
4.7
通讯作者：
Sheu JJ
中科院分区：
文献类型：
--
作者：
Chang CY;Chiang AJ;Yan MJ;Lai MT;Su YY;Huang HY;Chang CY;Li YH;Li PF;Chen CM;Hwang T;Hogg C;Greaves E;Sheu JJ
核糖体生物合成是细胞生长和增殖过程中蛋白质稳态的关键细胞过程。我们先前的研究证实了核糖体生物合成在子宫内膜异位症进展和恶变过程中上调，因此抗核糖体生物合成可能对治疗子宫内膜异位症及其相关并发症有效。建立了具有人类子宫内膜异位症特征的小鼠模型，并用三种不同的药物治疗，这些药物可以阻断核糖体生物合成，包括针对mTOR/PI 3 K（GSK 2126458）和RNA聚合酶I（CX 5461和BMH 21）的抑制剂。与溶剂处理的对照组相比，处理小鼠的平均病变数量和疾病频率显著降低。流式细胞术分析证实了小腹膜巨噬细胞和中性粒细胞群体的减少，大与小巨噬细胞比率增加，表明药物治疗抑制了炎症。治疗小鼠的病变也显示出较低的神经纤维密度，这可以支持通过行为研究发现的疼痛缓解。因此，我们的研究建议核糖体生物合成作为治疗子宫内膜异位症的潜在治疗靶点。
Ribosome biogenesis is a cellular process critical for protein homeostasis during cell growth and multiplication. Our previous study confirmed up-regulation of ribosome biogenesis during endometriosis progression and malignant transition, thus anti-ribosome biogenesis may be effective for treating endometriosis and the associated complications. A mouse model with human endometriosis features was established and treated with three different drugs that can block ribosome biogenesis, including inhibitors against mTOR/PI3K (GSK2126458) and RNA polymerase I (CX5461 and BMH21). The average lesion numbers and disease frequencies were significantly reduced in treated mice as compared to controls treated with vehicle. Flow cytometry analyses confirmed the reduction of small peritoneal macrophage and neutrophil populations with increased large versus small macrophage ratios, suggesting inflammation suppression by drug treatments. Lesions in treated mice also showed lower nerve fiber density which can support the finding of pain-relief by behavioral studies. Our study therefore suggested ribosome biogenesis as a potential therapeutic target for treating endometriosis.
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影响因子：
3.3
作者：
Chernoff, N.;Rogers, E. H.;Zehr, R. D.;Gage, M. I.;Malarkey, D. E.;Bradfield, C. A.;Liu, Y.;Schmid, J. E.;Jaskot, R. H.;Richards, J. H.;Wood, C. R.;Rosen, M. B.
通讯作者：
Rosen, M. B.
DOI：
10.1002/path.4657
发表时间：
2016-01
期刊：
The Journal of pathology
影响因子：
--
作者：
King CM;Barbara C;Prentice A;Brenton JD;Charnock-Jones DS
通讯作者：
Charnock-Jones DS
影响因子：
8
作者：
通讯作者：
--
影响因子：
3.8
作者：
de Arellano, Maria Luisa Barcena;Arnold, Julia;Mechsner, Sylvia
通讯作者：
Mechsner, Sylvia
抑制RNA聚合酶I作为促进p53癌症特异性激活的治疗策略。
影响因子：
50.3
作者：
Bywater MJ;Poortinga G;Sanij E;Hein N;Peck A;Cullinane C;Wall M;Cluse L;Drygin D;Anderes K;Huser N;Proffitt C;Bliesath J;Haddach M;Schwaebe MK;Ryckman DM;Rice WG;Schmitt C;Lowe SW;Johnstone RW;Pearson RB;McArthur GA;Hannan RD
通讯作者：
Hannan RD