Recombinant human platelet-derived growth factor enhanced dermal wound heating by a pathway involving ERK and c-fos in diabetic rats
Recombinant human platelet-derived growth factor enhanced dermal wound heating by a pathway involving ERK and c-fos in diabetic rats
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DOI：
10.1016/j.jdermsci.2006.11.014
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发表时间：
2007-03-01
影响因子：
4.6
通讯作者：
Sheng, Zhi-Yong
中科院分区：
文献类型：
--
作者：
Cheng, Biao;Liu, Hong-Wei;Sheng, Zhi-Yong
背景资料：血小板源性生长因子（Platetet-derived growth factor，PDGF）可促进皮肤创面加热，但其分子机制尚未完全阐明。目的：探讨PDGF促进糖尿病大鼠皮肤创面加热的可能信号转导机制。动物在受伤后1天每天用或不用重组人PDGF（rhPDGF）以7.0 μ g/cm（2）伤口或载体处理。伤后不同时间处死动物，取伤后皮肤组织进行组织学观察、细胞外信号调节激酶（ERK）磷酸化、c-fos蛋白表达及增殖细胞核抗原（PCNA）标记指数分析。伤后7天，局部应用rhPDGF与赋形剂治疗组或未治疗组相比显著加快了再上皮化的速率。在组织学水平上，伤后7、14 d，rhPDGF治疗组创面上皮再生程度、肉芽组织厚度和毛细血管芽密度均明显增加。结论：rhPDGF可促进糖尿病大鼠皮肤损伤后细胞增殖，促进皮肤组织修复，其机制可能与ERK激活和c-fos蛋白表达有关。(c)2006年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Platetet-derived growth factor (PDGF) has been shown to promote dermal wound heating, however, the molecular mechanisms responsible for are not fully understood.Objective: The present study was undertaken to investigate the possible signaling mechanisms by which PDGF improved heating of cutaneous wound in diabetic rats.Methods: Four full-thickness skin wounds were created on the dorsum of Wistar diabetic rats. Animals were treated with or without recombinant human PDGF (rhPDGF) at 7.0 mu g/cm(2) wound or vehicle daily 1 day after wounding. The animals were then killed after various intervals of wounding, and the wounded skin tissues were used for histological evaluation, analysis of the phosphorylation of extracellular signal-regulated kinases (ERK) and the expression of c-fos protein, as well as the labeling indices of proliferative cell nuclear antigen (PCNA).Results: Topical application of rhPDGF significantly accelerated the rate of reepithetiatization compared with vehicle-treated or untreated group at 7 days after wounding. At the histological level, the significant increases in the degree of reepithelialization, the thickness of granulation tissue and the density of capillary bud were observed in the wound sites in rhPDGF-treated group at 7 and 14 days after wounding. Moreover, treatment with rhPDGF increased PCNA labeling indices, c-fos protein expression and ERK phosphorylation in the wounded tissues at the indicated time after wounding.Conclusion: These results suggest that application of rhPDGF increases cell proliferation, and enhances dermal tissue repair in diabetic skin lesion of rats, which might be partly mediated by ERK activation and c-fos protein expression. (c) 2006 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.