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新型基因沉默吡咯-咪唑聚酰胺抑制糖尿病肾病，防止 USF1 与 TGF-β1 启动子结合。

Transcriptional Suppression of Diabetic Nephropathy with Novel Gene Silencer Pyrrole-Imidazole Polyamides Preventing USF1 Binding to the TGF-β1 Promoter.

机构信息

Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Ooyaguchi-kami 30-1, Itabashi-ku, Tokyo 173-8610, Japan.

Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo 173-8610, Japan.

出版信息

Int J Mol Sci. 2021 Apr 29;22(9):4741. doi: 10.3390/ijms22094741.

DOI:10.3390/ijms22094741
PMID:33947045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8125144/
Abstract

Upstream stimulatory factor 1 (USF1) is a transcription factor that is increased in high-glucose conditions and activates the transforming growth factor (TGF)-β1 promoter. We examined the effects of synthetic pyrrole-imidazole (PI) polyamides in preventing USF1 binding on the TGF-β1 promoter in Wistar rats in which diabetic nephropathy was established by intravenous administration of streptozotocin (STZ). High glucose induced nuclear localization of USF1 in cultured mesangial cells (MCs). In MCs with high glucose, USF1 PI polyamide significantly inhibited increases in promoter activity of TGF-β1 and expression of TGF-β1 mRNA and protein, whereas it significantly decreased the expression of osteopontin and increased that of -caldesmon mRNA. We also examined the effects of USF1 PI polyamide on diabetic nephropathy. Intraperitoneal injection of USF1 PI polyamide significantly suppressed urinary albumin excretion and decreased serum urea nitrogen in the STZ-diabetic rats. USF1 PI polyamide significantly decreased the glomerular injury score and tubular injury score in the STZ-diabetic rats. It also suppressed the immunostaining of TGF-β1 in the glomerulus and proximal tubules and significantly decreased the expression of TGF-β1 protein from kidney in these rats. These findings indicate that synthetic USF1 PI polyamide could potentially be a practical medicine for diabetic nephropathy.

摘要

上游刺激因子 1（USF1）是一种转录因子，在高糖条件下增加，并激活转化生长因子（TGF）-β1 启动子。我们研究了合成吡咯-咪唑（PI）聚酰胺在预防糖尿病肾病大鼠静脉注射链脲佐菌素（STZ）所致糖尿病肾病中 USF1 结合 TGF-β1 启动子的作用。高葡萄糖诱导培养的肾小球系膜细胞（MCs）中 USF1 的核定位。在高葡萄糖的 MCs 中，USF1 PI 聚酰胺显著抑制 TGF-β1 启动子活性和 TGF-β1 mRNA 和蛋白表达的增加，而显著降低骨桥蛋白的表达并增加 -钙调蛋白 mRNA 的表达。我们还研究了 USF1 PI 聚酰胺对糖尿病肾病的影响。USF1 PI 聚酰胺的腹腔注射显著抑制了 STZ 糖尿病大鼠的尿白蛋白排泄，并降低了血清尿素氮。USF1 PI 聚酰胺显著降低了 STZ 糖尿病大鼠的肾小球损伤评分和肾小管损伤评分。它还抑制了肾小球和近端小管中 TGF-β1 的免疫染色，并显著降低了这些大鼠肾脏中 TGF-β1 蛋白的表达。这些发现表明，合成的 USF1 PI 聚酰胺可能是一种治疗糖尿病肾病的实用药物。

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本文引用的文献

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2
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Molecules. 2019 Sep 1;24(17):3178. doi: 10.3390/molecules24173178.
3
Isoform-specific effects of transforming growth factor β on endothelial-to-mesenchymal transition.
转化生长因子 β 异构体对血管内皮细胞向间充质细胞转化的影响。
J Cell Physiol. 2018 Nov;233(11):8418-8428. doi: 10.1002/jcp.26801. Epub 2018 Jun 1.
4
Osteopontin activates mesenchymal stem cells to repair skin wound.骨桥蛋白激活间充质干细胞以修复皮肤伤口。
PLoS One. 2017 Sep 28;12(9):e0185346. doi: 10.1371/journal.pone.0185346. eCollection 2017.
5
Obesity, oxidative stress, and fibrosis in chronic kidney disease.慢性肾脏病中的肥胖、氧化应激与纤维化
Kidney Int Suppl (2011). 2014 Nov;4(1):113-117. doi: 10.1038/kisup.2014.21.
6
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Semin Nephrol. 2012 May;32(3):261-8. doi: 10.1016/j.semnephrol.2012.04.005.
7
Regulation of endothelial cell plasticity by TGF-β.TGF-β 对血管内皮细胞可塑性的调节。
Cell Tissue Res. 2012 Jan;347(1):177-86. doi: 10.1007/s00441-011-1222-6. Epub 2011 Aug 25.
8
Role of the USF1 transcription factor in diabetic kidney disease.USF1 转录因子在糖尿病肾病中的作用。
Am J Physiol Renal Physiol. 2011 Aug;301(2):F271-9. doi: 10.1152/ajprenal.00221.2011. Epub 2011 May 4.
9
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10
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