Miragliotta V, Pirone A, Donadio E, Abramo F, Ricciardi M P, Theoret C L
Department of Veterinary Sciences, University of Pisa, Pisa, Italy.
Department of Pharmacy, University of Pisa, Pisa, Italy.
Equine Vet J. 2016 Jan;48(1):72-7. doi: 10.1111/evj.12372. Epub 2014 Dec 18.
Convincing evidence shows that persistent or excessive expression of osteopontin (OPN) is linked to fibroproliferation of various organs in laboratory animals and in man, such that its downregulation is a logical therapeutic objective.
To investigate OPN expression in an equine model of wound healing and in clinical specimens of equine exuberant granulation tissue and human keloids in an effort to better understand the contribution of this protein to inflammation-associated skin fibrosis.
Description of gene and protein expression in an experimental equine model of wound healing and clinical specimens in horse and man.
Osteopontin gene expression was evaluated by quantitative PCR, while protein expression was investigated by means of immunohistochemical staining.
Quantitative PCR showed that the OPN gene is expressed in normal intact skin of horses and continues to be expressed during the wound-healing process. An increase in gene expression was observed throughout the phases of wound healing, with a final decrease at wound closure. The protein was not detected in normal skin. Keratinocytes in wound-edge samples did not express the protein, whereas dermal immunoreactivity was confined to inflammatory cells. Healed wounds were devoid of staining. Equine exuberant granulation tissue showed immunoreactivity of the surrounding epidermis, infiltrating neutrophils, mononuclear cells, endothelial cells and fibroblasts. Human keloids showed OPN immunoreactivity throughout the epidermis as well as in mononuclear cells and scattered fibroblasts.
Immunohistochemical data show a different pattern of expression between normally healing and fibrotic wounds (exuberant granulation tissue and keloids), thus suggesting a role in fibroproliferation in horses and man.
确凿证据表明，骨桥蛋白（OPN）的持续或过度表达与实验动物及人类多种器官的纤维增生有关，因此下调其表达是合理的治疗目标。
研究骨桥蛋白在马伤口愈合模型、马增生性肉芽组织临床标本及人类瘢痕疙瘩中的表达情况，以更好地了解该蛋白在炎症相关皮肤纤维化中的作用。
描述马伤口愈合实验模型以及马和人类临床标本中的基因和蛋白表达情况。
通过定量PCR评估骨桥蛋白基因表达，采用免疫组织化学染色研究蛋白表达。
定量PCR显示，OPN基因在马的正常完整皮肤中表达，并在伤口愈合过程中持续表达。在伤口愈合的各个阶段均观察到基因表达增加，在伤口闭合时最终下降。在正常皮肤中未检测到该蛋白。伤口边缘样本中的角质形成细胞不表达该蛋白，而真皮免疫反应仅限于炎症细胞。愈合的伤口无染色。马增生性肉芽组织显示周围表皮、浸润的中性粒细胞、单核细胞、内皮细胞和成纤维细胞有免疫反应性。人类瘢痕疙瘩在整个表皮以及单核细胞和散在的成纤维细胞中均显示OPN免疫反应性。
免疫组织化学数据显示正常愈合伤口与纤维化伤口（增生性肉芽组织和瘢痕疙瘩）之间存在不同的表达模式，因此提示其在马和人类的纤维增生中发挥作用。
