Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scars in a Common Marmoset Primate Model.
Preclinical Study of Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Human TGF-β1 Promoter for Hypertrophic Scars in a Common Marmoset Primate Model.
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DOI：
10.1371/journal.pone.0125295
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Soma M
中科院分区：
文献类型：
--
作者：
Igarashi J;Fukuda N;Inoue T;Nakai S;Saito K;Fujiwara K;Matsuda H;Ueno T;Matsumoto Y;Watanabe T;Nagase H;Bando T;Sugiyama H;Itoh T;Soma M
我们报告了一项临床前研究的吡咯-咪唑（PI）聚酰胺，靶向人转化生长因子（hTGF）-β1基因作为一种新的转录基因沉默子在一个共同的绒猴灵长类动物模型。我们设计并合成了PI聚酰胺以靶向hTGF-β1启动子。我们研究了七种PI聚酰胺（GB 1101 -1107）对佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）刺激的人血管平滑肌细胞hTGF-β1 mRNA表达的影响。GB 1101、GB 1105和GB 1106可显著抑制hTGF-β1 mRNA的表达。我们在体内研究了GB 1101作为hTGF-β1的PI聚酰胺对绒猴增生性瘢痕的作用。注射GB 1101可在术后35天完全抑制增生性瘢痕的形成，并抑制细胞浸润、TGF-β1和波形蛋白染色以及表皮厚度。不匹配的聚酰胺不影响增生性瘢痕形成或组织学变化。与水和错配PI聚酰胺相比，使用GB 1101的表皮显著更薄。我们开发了PI聚酰胺用于治疗增生性瘢痕的实用软膏药物。FITC标记的GB 1101与solbase最有效地分布在表皮角质形成细胞的细胞核中，在切口后42天完全抑制增生性瘢痕形成，并显著抑制表皮厚度和波形蛋白阳性成纤维细胞。以hTGF-β1启动子为靶点的PI聚酰胺与solbase软膏联合应用，有望成为治疗手术后增生性瘢痕和烧伤后增生性瘢痕的实用药物。
We report a preclinical study of a pyrrole-imidazole (PI) polyamide that targets the human transforming growth factor (hTGF)-β1 gene as a novel transcriptional gene silencer in a common marmoset primate model. We designed and then synthesized PI polyamides to target the hTGF-β1 promoter. We examined effects of seven PI polyamides (GB1101-1107) on the expression of hTGF-β1 mRNA stimulated with phorbol 12-myristate 13-acetate (PMA) in human vascular smooth muscle cells. GB1101, GB1105 and GB1106 significantly inhibited hTGF-β1 mRNA expression. We examined GB1101 as a PI polyamide to hTGF-β1 for hypertrophic scars in marmosets in vivo. Injection of GB1101 completely inhibited hypertrophic scar formation at 35 days post-incision and inhibited cellular infiltration, TGF-β1 and vimentin staining, and epidermal thickness. Mismatch polyamide did not affect hypertrophic scarring or histological changes. Epidermis was significantly thinner with GB1101 than with water and mismatch PI polyamides. We developed the PI polyamides for practical ointment medicines for the treatment of hypertrophic scars. FITC-labeled GB1101 with solbase most efficiently distributed in the nuclei of epidermal keratinocytes, completely suppressed hypertropic scarring at 42 days after incision, and considerably inhibited epidermal thickness and vimentin-positive fibroblasts. PI polyamides targeting hTGF-β1 promoter with solbase ointment will be practical medicines for treating hypertrophic scars after surgical operations and skin burns.
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DOI：
10.1124/jpet.105.089086
发表时间：
2005-11-01
影响因子：
3.5
作者：
Lai, YM;Fukuda, N;Serie, K
通讯作者：
Serie, K
影响因子：
64.8
作者：
Trauger, JW;Baird, EE;Dervan, PB
通讯作者：
Dervan, PB
影响因子：
6.9
作者：
Zhao, Rui;Yan, Qitao;Ma, Wenli
通讯作者：
Ma, Wenli
影响因子：
13.6
作者：
Fukuda, Noboru;Ueno, Takahiro;Serie, Kazuo
通讯作者：
Serie, Kazuo
DOI：
10.1177/1534734608320786
发表时间：
2008-09-01
期刊：
The international journal of lower extremity wounds
影响因子：
--
作者：
Roques, Claude;Teot, Luc
通讯作者：
Teot, Luc