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对比浅层和深层部分厚度烧伤创面的约克夏猪和红杜洛克猪的转录组分析。

Comparative Transcriptome Analysis of Superficial and Deep Partial-Thickness Burn Wounds in Yorkshire vs Red Duroc Pigs.

机构信息

Division of Combat Wound Repair, US Army Institute of Surgical Research, JBSA Fort Sam Houston, TX, USA.

Greehey Children's Cancer Research Institute, University of Texas - Health San Antonio, TX, USA.

出版信息

J Burn Care Res. 2022 Nov 2;43(6):1299-1311. doi: 10.1093/jbcr/irac028.

Abstract

Hypertrophic scars are a common negative outcome of deep partial-thickness (DPT) burn wounds resulting in increased dermal thickness, wound area contracture, and inflammation of the affected area. The red Duroc and Yorkshire porcine breeds are common large animal models for studying dermal wounds due to their structural similarities to human skin; however, the porcine transcriptomic profiles of dermal burn wounds and healing process are not well known. In response, a longitudinal transcriptomic comparative study was conducted comparing red Duroc and Yorkshire superficial and DPT burn wounds to their respective control uninjured tissue. Using next-generation RNA sequencing, total RNAs were isolated from burn wound tissue harvested on 0, 3, 7, 15, 30, and 60 days postburn, and mRNA-seq and gene expression read counts were generated. Significant differentially expressed genes relative to uninjured tissue were defined, and active biological processes were determined using gene set enrichment analyses. Additionally, collagen deposition, α-smooth muscle actin (SMA) protein concentration, epidermal and dermal thickness measurements, and wound area changes in response to burn injury were characterized. Overall, the red Duroc pigs, in response to both burn wound types, elicited a more robust and prolonged inflammatory immune response, fibroblast migration, and proliferation, as well as heightened levels of extracellular matrix modulation relative to respective burn types in the Yorkshire pigs. Collectively, the red Duroc DPT burn wounds produce a greater degree of hypertrophic scar-like response compared with Yorkshire DPT burn wounds. These findings will facilitate future porcine burn studies down-selecting treatment targets and determining the effects of novel therapeutic strategies.

摘要

增生性瘢痕是深度部分厚度(DPT)烧伤创面的常见不良后果,导致真皮增厚、创面面积挛缩和受影响区域的炎症。红色杜洛克和约克夏猪是研究皮肤创面的常见大型动物模型,因为它们的结构与人皮肤相似;然而,猪皮肤烧伤创面和愈合过程的转录组特征尚不清楚。为此,进行了一项纵向转录组比较研究,比较了红色杜洛克和约克夏猪的皮肤浅层和 DPT 烧伤创面与其各自的未受伤组织。使用下一代 RNA 测序,从烧伤后 0、3、7、15、30 和 60 天收获的烧伤创面组织中分离总 RNA,并生成 mRNA-seq 和基因表达读数。相对于未受伤组织,定义了显著差异表达的基因,并使用基因集富集分析确定了活跃的生物学过程。此外,还对胶原沉积、α-平滑肌肌动蛋白(SMA)蛋白浓度、表皮和真皮厚度测量以及烧伤后创面面积变化进行了表征。总的来说,红色杜洛克猪对两种烧伤类型都产生了更强烈和持久的炎症免疫反应、成纤维细胞迁移和增殖,以及更高水平的细胞外基质调节,相对于约克夏猪的相应烧伤类型。总之,红色杜洛克猪的 DPT 烧伤创面比约克夏猪的 DPT 烧伤创面产生更严重的增生性瘢痕样反应。这些发现将促进未来的猪烧伤研究,选择治疗靶点,并确定新型治疗策略的效果。

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本文引用的文献

1
The Biology of Extracellular Matrix Proteins in Hypertrophic Scarring.肥厚性瘢痕中细胞外基质蛋白的生物学
Adv Wound Care (New Rochelle). 2022 May;11(5):234-254. doi: 10.1089/wound.2020.1257. Epub 2021 Jul 5.
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Burn injury.烧伤
Nat Rev Dis Primers. 2020 Feb 13;6(1):11. doi: 10.1038/s41572-020-0145-5.
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Update on the Treatment of Scars.瘢痕治疗的最新进展
J Drugs Dermatol. 2019 Jun 1;18(6):550-555.
4

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