A novel immune competent murine hypertrophic scar contracture model: a tool to elucidate disease mechanism and develop new therapies.
A novel immune competent murine hypertrophic scar contracture model: a tool to elucidate disease mechanism and develop new therapies.
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DOI：
10.1111/wrr.12238
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Levinson H
中科院分区：
文献类型：
--
作者：
Ibrahim MM;Bond J;Bergeron A;Miller KJ;Ehanire T;Quiles C;Lorden ER;Medina MA;Fisher M;Klitzman B;Selim MA;Leong KW;Levinson H
烧伤后增生性瘢痕（HSc）收缩导致挛缩。挛缩是痛苦和毁容。目前的治疗方法效果甚微。为了研究发病机制和开发新的治疗方法，需要小鼠模型。我们已经创建了经验证的免疫活性鼠HSc模型。在C57 BL/6小鼠的背部上产生三度烧伤。烧伤后3天，切除组织并与耳皮肤移植。分析移植物收缩，并在不同时间点收获组织。将结果与人体状况进行比较，以验证模型。为了确认移植物存活，使用绿色荧光蛋白（GFP）小鼠，并进行组织学分析以区分耳和背部皮肤。分析了肌脂膜在收缩中的作用。用4′，6-二脒基-2-苯基吲哚评估细胞构成。用苦天狼星红评估胶原成熟。肥大细胞甲苯胺蓝染色。用F4/80免疫检测巨噬细胞。用CD 31免疫法评估血管性。通过定量实时聚合酶链反应（qRT-PCR）检测收缩蛋白的RNA。使用微应变分析仪分析皮肤和瘢痕组织的弹性模量。移植物在第14天收缩至其原始大小的45%，并保持其大小。将GFP小鼠皮肤移植到野生型小鼠上，并分析真皮厚度和毛囊密度，证实了移植物存活。有趣的是，毛囊在移植后消失，并在第30天在耳皮肤构型中再生。放射学分析显示肉脂膜不参与收缩。显微镜分析显示移植物显示细胞结构增加。第3天后形成肉芽组织。胶原蛋白分析显示胶原蛋白成熟随时间增加。CD 31染色显示血管增多。巨噬细胞和肥大细胞增多。qRT-PCR显示HSc中转化生长因子β、α平滑肌肌动蛋白和rho相关蛋白激酶2上调。拉伸测试显示，人类皮肤和疤痕组织比小鼠皮肤和疤痕组织更坚韧。
Hypertrophic scar (HSc) contraction following burn injury causes contractures. Contractures are painful and disfiguring. Current therapies are marginally effective. To study pathogenesis and develop new therapies, a murine model is needed. We have created a validated immune-competent murine HSc model. A third-degree burn was created on dorsum of C57BL/6 mice. Three days postburn, tissue was excised and grafted with ear skin. Graft contraction was analyzed and tissue harvested on different time points. Outcomes were compared with human condition to validate the model. To confirm graft survival, green fluorescent protein (GFP) mice were used, and histologic analysis was performed to differentiate between ear and back skin. Role of panniculus carnosus in contraction was analyzed. Cellularity was assessed with 4′,6-diamidino-2-phenylindole. Collagen maturation was assessed with Picro-sirius red. Mast cells were stained with Toluidine blue. Macrophages were detected with F4/80 immune. Vascularity was assessed with CD31 immune. RNA for contractile proteins was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Elastic moduli of skin and scar tissue were analyzed using a microstrain analyzer. Grafts contracted to ∼45% of their original size by day 14 and maintained their size. Grafting of GFP mouse skin onto wild-type mice, and analysis of dermal thickness and hair follicle density, confirmed graft survival. Interestingly, hair follicles disappeared after grafting and regenerated in ear skin configuration by day 30. Radiological analysis revealed that panniculus carnosus doesn't contribute to contraction. Microscopic analyses showed that grafts show increase in cellularity. Granulation tissue formed after day 3. Collagen analysis revealed increases in collagen maturation over time. CD31 stain revealed increased vascularity. Macrophages and mast cells were increased. qRT-PCR showed up-regulation of transforming growth factor beta, alpha smooth muscle actin, and rho-associated protein kinase 2 in HSc. Tensile testing revealed that human skin and scar tissues are tougher than mouse skin and scar tissues.
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影响因子：
3.4
作者：
Arbab MH;Dickey TC;Winebrenner DP;Chen A;Klein MB;Mourad PD
通讯作者：
Mourad PD
影响因子：
4.8
作者：
Chihara, K;Amano, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
DOI：
10.1083/jcb.117.1.73
发表时间：
1992-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kolodney MS;Wysolmerski RB
通讯作者：
Wysolmerski RB
影响因子：
3.4
作者：
Hara, M;Ono, K;Matsumori, A
通讯作者：
Matsumori, A
影响因子：
4.8
作者：
Aarabi, Shahram;Bhatt, Kirit A.;Gurtner, Geoffrey C.
通讯作者：
Gurtner, Geoffrey C.