Growth factors in porcine full and partial thickness burn repair. Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and neu differentiation factor.

Growth factors in porcine full and partial thickness burn repair. Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and neu differentiation factor.
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生长因子在猪全层和部分厚度烧伤修复中的作用。

DOI:
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发表时间:
1995
影响因子:
6
通讯作者:
Glenn F. Pierce
Glenn F. Pierce
中科院分区:
医学2区
文献类型:
--
作者:
D. Danilenko;B. D. Ring;J. Tarpley;Barry Morris;Gwyneth Y. Van;Andrew Morawiecki;William Callahan;Merrill Goldenberg;Susan Hershenson;Glenn F. Pierce

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局部应用重组生长因子,如表皮生长因子、血小板源性生长因子-BB 同二聚体 (rPDGF-BB)、角质形成细胞生长因子 (rKGF) 和 neu 分化因子,已在多种伤口修复动物模型中显着加速愈合。在这项研究中,我们建立了高度可重复和可量化的全层和深层猪烧伤模型,其中烧伤后 4 或 5 天切除烧痂并用封闭敷料覆盖,以复制人类烧伤患者的标准治疗。然后,我们应用这些生长因子来评估它们对伤口修复的几个参数的功效:细胞外基质和肉芽组织的产生、再上皮化百分比和新上皮面积。在全层烧伤中,仅rPDGF-BB以及rPDGF-BB和rKGF的组合诱导烧伤修复的显着变化。 rPDGF-BB 诱导显着的细胞外基质和肉芽组织产生(P = 0.013),使得烧伤缺损在切痂后几天内被填充,但对新上皮区域或上皮再生没有影响。 rPDGF-BB和rKGF联合治疗全层烧伤导致细胞外基质和肉芽组织面积显着增加(P = 0.0009)和新上皮面积显着增加(P = 0.007),但对再上皮化没有影响。在深度部分厚度烧伤中,rKGF 引起最一致的变化。每日使用rKGF可诱导新上皮面积显着增加(P < 0.0001),但仅诱导烧伤后12天的再上皮化适度增加(rKGF治疗组为83.7%,对照组为70.2%;P = 0.016)。 rKGF 还使烧伤后 13 天完全再上皮烧伤的数量增加了一倍(P = 0.02),至少部分是因为通过增殖细胞核抗原表达评估,显着刺激了表皮和毛囊增殖。对猪烧伤中 KGFR 的原位杂交显示,KGFR 在毛囊和基底表皮上强烈表达,证实了 rKGF 对毛囊和表皮角质形成细胞的直接作用。尽管rKGF诱导的上皮增殖导致明显的新表皮银屑病样增生,并伴有夸张的网状脊,并且根据细胞角蛋白10的表达评估,新表皮和毛囊成熟,但在一些rKGF治疗的烧伤中,角质形成细胞终末分化的标志物并未延迟,并且似乎加速。重组表皮生长因子在深度部分厚度烧伤中诱导新上皮面积增加的趋势,但对上皮再生没有影响。重组神经分化因子-α 2 亚型对全层或深部烧伤没有显着的生物学效应。(摘要截断为 250 字)
The topical application of recombinant growth factors such as epidermal growth factor, platelet-derived growth factor-BB homodimer (rPDGF-BB), keratinocyte growth factor (rKGF), and neu differentiation factor has resulted in significant acceleration of healing in several animal models of wound repair. In this study, we established highly reproducible and quantifiable full and deep partial thickness porcine burn models in which burns were escharectomized 4 or 5 days postburn and covered with an occlusive dressing to replicate the standard treatment in human burn patients. We then applied these growth factors to assess their efficacy on several parameters of wound repair: extracellular matrix and granulation tissue production, percent reepithelialization, and new epithelial area. In full thickness burns, only rPDGF-BB and the combination of rPDGF-BB and rKGF induced significant changes in burn repair. rPDGF-BB induced marked extracellular matrix and granulation tissue production (P = 0.013) such that the burn defect was filled within several days of escharectomy, but had no effect on new epithelial area or reepithelialization. The combination of rPDGF-BB and rKGF in full thickness burns resulted in a highly significant increase in extracellular matrix and granulation tissue area (P = 0.0009) and a significant increase in new epithelial area (P = 0.007), but had no effect on reepithelialization. In deep partial thickness burns, rKGF induced the most consistent changes. Daily application of rKGF induced a highly significant increase in new epithelial area (P < 0.0001) but induced only a modest increase in reepithelialization (83.7% rKGF-treated versus 70.2% control; P = 0.016) 12 days postburn. rKGF also doubled the number of fully reepithelialized burns (P = 0.02) at 13 days postburn, at least partially because of marked stimulation of both epidermal and follicular proliferation as assessed by proliferating cell nuclear antigen expression. In situ hybridization for KGFR in porcine burns revealed strong expression of KGFR on hair follicles and basal epidermis, confirming direct rKGF action on follicular as well as epidermal keratinocytes. Although the epithelial proliferation induced by rKGF resulted in marked neoepidermal psoriasiform hyperplasia with exaggerated rete ridges and neoepidermal and follicular maturation as assessed by expression of cytokeratin 10, a marker of keratinocyte terminal differentiation was not delayed and appeared to be accelerated in some rKGF-treated burns. Recombinant epidermal growth factor induced a trend toward increased new epithelial area in deep partial thickness burns, but had no effect on reepithelialization. The recombinant neu differentiation factor-alpha 2 isoform had no significant biological effects in either full or deep partial thickness burns.(ABSTRACT TRUNCATED AT 250 WORDS)
DOI: --
发表时间: 1992-06
期刊: The American journal of pathology
影响因子: --
作者:
G. Pierce;J. Tarpley;D. Yanagihara;Thomas A. Mustoe, MD, FACS;G. M. Fox;A. Thomason
通讯作者: G. Pierce;J. Tarpley;D. Yanagihara;Thomas A. Mustoe, MD, FACS;G. M. Fox;A. Thomason
DOI: 10.1172/jci116673
发表时间: 1993-08-01
影响因子: 15.9
作者:
PANOS, RJ;RUBIN, JS;MASON, RJ
通讯作者: MASON, RJ
DOI: 10.1126/science.6304883
发表时间: 1983-01-01
期刊: SCIENCE
影响因子: 56.9
作者:
DOOLITTLE, RF;HUNKAPILLER, MW;ANTONIADES, HN
通讯作者: ANTONIADES, HN
DOI: --
发表时间: 1993
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Molloy,RG;O'Riordain,M;Holzheimer,R;Nestor,M;Collins,K;Mannick,JA;Rodrick,ML
通讯作者: Rodrick,ML
DOI: 10.1172/jci115048
发表时间: 1991-02-01
影响因子: 15.9
作者:
MUSTOE, TA;PIERCE, GF;DEUEL, TF
通讯作者: DEUEL, TF