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他莫昔芬的给药可调节创伤性脊髓损伤急性期基因表达的变化。

Administration of Tamoxifen Can Regulate Changes in Gene Expression during the Acute Phase of Traumatic Spinal Cord Injury.

作者信息

Cabrera-Aldana Eibar E, Balderas-Martinez Yalbi I, Velázquez-Cruz Rafael, Tovar-Y-Romo Luis B, Sevilla-Montoya Rosalba, Martínez-Cruz Angelina, Martinez-Cordero Claudia, Valdes-Flores Margarita, Santamaria-Olmedo Monica, Hidalgo-Bravo Alberto, Guízar-Sahagún Gabriel

机构信息

Department of Genomics Medicine, National Institute of Rehabilitation (INR), Calzada Mexico-Xochimilco 289, Arenal de Guadalupe, Mexico City 14389, Mexico.

Laboratorio de Biología Computacional, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Calz. de Tlalpan 4502, Belisario Domínguez Secc 16, Tlalpan, Mexico City 14080, Mexico.

出版信息

Curr Issues Mol Biol. 2023 Sep 13;45(9):7476-7491. doi: 10.3390/cimb45090472.

DOI:10.3390/cimb45090472
PMID:37754256
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10529143/
Abstract

Traumatic spinal cord injury (SCI) causes irreversible damage leading to incapacity. Molecular mechanisms underlying SCI damage are not fully understood, preventing the development of novel therapies. Tamoxifen (TMX) has emerged as a promising therapy. Our aim was to identify transcriptome changes in the acute phase of SCI and the effect of Tamoxifen on those changes in a rat model of SCI. Four groups were considered: (1) Non-injured without TMX (Sham/TMX-), (2) Non-injured with TMX (Sham/TMX+), (3) injured without TMX (SCI/TMX-), and (4) injured with TMX (SCI/TMX+). Tamoxifen was administered intraperitoneally 30 min after injury, and spinal cord tissues were collected 24 h after injury. Clariom S Assays Array was used for transcriptome analysis. After comparing Sham/TMX- versus SCI/TMX-, 708 genes showed differential expression. The enriched pathways were the SCI pathway and pathways related to the inflammatory response. When comparing SCI/TMX- versus SCI/TMX+, only 30 genes showed differential expression, with no pathways enriched. Our results showed differential expression of genes related to the inflammatory response after SCI, and Tamoxifen seems to regulate gene expression changes in and . Our study contributes data regarding the potential value of tamoxifen as a therapeutic resource for traumatic SCI during the acute phase.

摘要

创伤性脊髓损伤（SCI）会导致不可逆转的损伤，进而导致残疾。SCI损伤的分子机制尚未完全明确，这阻碍了新型疗法的开发。他莫昔芬（TMX）已成为一种有前景的治疗方法。我们的目的是确定SCI急性期的转录组变化以及他莫昔芬对SCI大鼠模型中这些变化的影响。研究考虑了四组：（1）未受伤且未使用他莫昔芬（假手术/TMX-），（2）未受伤且使用他莫昔芬（假手术/TMX+），（3）受伤且未使用他莫昔芬（SCI/TMX-），以及（4）受伤且使用他莫昔芬（SCI/TMX+）。在损伤后30分钟腹腔注射他莫昔芬，并在损伤后24小时收集脊髓组织。使用Clariom S分析阵列进行转录组分析。比较假手术/TMX-组与SCI/TMX-组后，有708个基因表现出差异表达。富集的通路是SCI通路和与炎症反应相关的通路。比较SCI/TMX-组与SCI/TMX+组时，只有30个基因表现出差异表达，没有富集的通路。我们的结果显示SCI后与炎症反应相关的基因存在差异表达，并且他莫昔芬似乎调节了[此处原文缺失相关内容]中的基因表达变化。我们的研究提供了有关他莫昔芬作为创伤性SCI急性期治疗资源的潜在价值的数据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/f1ed45591fd4/cimb-45-00472-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/ff3138483701/cimb-45-00472-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/79281676b061/cimb-45-00472-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/a973b780fb73/cimb-45-00472-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/09ce4e2e1422/cimb-45-00472-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/5a619d37146e/cimb-45-00472-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/f1ed45591fd4/cimb-45-00472-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/ff3138483701/cimb-45-00472-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/79281676b061/cimb-45-00472-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/a973b780fb73/cimb-45-00472-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/09ce4e2e1422/cimb-45-00472-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/5a619d37146e/cimb-45-00472-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84bc/10529143/f1ed45591fd4/cimb-45-00472-g006.jpg

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