Travis Taryn E, Ghassemi Pejhman, Prindeze Nicholas J, Moffatt Lauren T, Carney Bonnie C, Alkhalil Abdulnaser, Ramella-Roman Jessica C, Shupp Jeffrey W
The Burn Center, Department of Surgery, MedStar Washington Hospital Center, Washington, DC.
Firefighters' Burn and Surgical Research Laboratory, MedStar Health Research Institute, Washington, DC.
Eplasty. 2018 Jan 5;18:e1. eCollection 2018.
Proteins of the matrix metalloproteinases family play a vital role in extracellular matrix maintenance and basic physiological processes in tissue homeostasis. The function and activities of matrix metalloproteinases in response to compression therapies have yet to be defined. Here, a swine model of hypertrophic scar was used to profile the transcription of all known 26 matrix metalloproteinases in scars treated with a precise compression dose. Full-thickness excisional wounds were created. Wounds underwent healing and scar formation. A subset of scars underwent 2 weeks of compression therapy. Biopsy specimens were preserved, and microarrays, reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry were performed to characterize the transcription and expression of various matrix metalloproteinase family members. Microarray results showed that 13 of the known 26 matrix metalloproteinases were differentially transcribed in wounds relative to the preinjury skin. The predominant upregulation of these matrix metalloproteinases during early wound-healing stages declined gradually in later stages of wound healing. The use of compression therapy reduced this decline in 10 of the 13 differentially regulated matrix metalloproteinases. Further investigation of MMP7 using reverse transcription-polymerase chain reaction confirmed the effect of compression on transcript levels. Assessment of MMP7 at the protein level using Western blotting and immunohistochemistry was concordant. In a swine model of hypertrophic scar, the application of compression to hypertrophic scar attenuated a trend of decreasing levels of matrix metalloproteinases during the process of hypertrophic wound healing, including MMP7, whose enzyme regulation was confirmed at the protein level.
基质金属蛋白酶家族的蛋白质在细胞外基质维持以及组织稳态的基本生理过程中发挥着至关重要的作用。基质金属蛋白酶在应对压迫疗法时的功能和活性尚未明确。在此,使用了一个肥厚性瘢痕的猪模型来分析在精确压迫剂量治疗的瘢痕中所有已知的26种基质金属蛋白酶的转录情况。制造了全层切除伤口。伤口经历愈合和瘢痕形成过程。一部分瘢痕接受了2周的压迫疗法。保存活检标本,并进行微阵列、逆转录-聚合酶链反应、蛋白质印迹和免疫组织化学,以表征各种基质金属蛋白酶家族成员的转录和表达。微阵列结果显示,在已知的26种基质金属蛋白酶中,有13种在伤口中的转录相对于伤前皮肤存在差异。这些基质金属蛋白酶在伤口愈合早期的主要上调在伤口愈合后期逐渐下降。压迫疗法的使用减少了13种差异调节的基质金属蛋白酶中10种的这种下降。使用逆转录-聚合酶链反应对MMP7进行进一步研究证实了压迫对转录水平的影响。使用蛋白质印迹和免疫组织化学在蛋白质水平对MMP7进行的评估结果一致。在肥厚性瘢痕的猪模型中,对肥厚性瘢痕施加压迫可减弱肥厚性伤口愈合过程中基质金属蛋白酶水平下降的趋势,包括MMP7,其酶调节在蛋白质水平得到证实。