生物谷報(bào)道：英國布里斯托爾大學(xué)（University of Bristol）的一項(xiàng)研究表明,，抑制一個(gè)基因就能使傷口愈合較快,，并減少疤痕,。這個(gè)發(fā)現(xiàn)重大的意義,，不僅對(duì)皮膚傷口,，而且對(duì)患病或腹部手術(shù)所造成的器官組織損傷都有重大意義,。
當(dāng)皮膚受損血塊形成時(shí)，傷口底下的細(xì)胞開始修復(fù)損傷,，導(dǎo)致疤痕的出現(xiàn),。疤痕是組織修復(fù)過程中自然出現(xiàn)的，在割傷或燒傷后的皮膚非常顯眼,。疤痕可能很小,，如膝蓋擦傷；也可能很大,，如糖尿病腿部潰瘍,。而且疤痕也不僅限于皮膚,。所有的組織修復(fù)是都會(huì)產(chǎn)生疤痕，比如說,，酒精性肝損傷會(huì)導(dǎo)致纖維化和肝功能衰竭,；腹部手術(shù)后的疤痕常可導(dǎo)致嚴(yán)重并發(fā)癥發(fā)生,。
組織損傷會(huì)誘發(fā)炎癥反應(yīng),，釋放白色細(xì)胞殺死微生物，以保護(hù)皮膚免受感染,。同樣是白色細(xì)胞引導(dǎo)膠原蛋白層的生成,，而這些膠原蛋白層幫助傷口愈合，但它們從周圍的皮膚突出來,，并造成疤痕,。布里斯托爾大學(xué)的Paul Martin教授及其同事的研究結(jié)果表明，骨橋蛋白（osteopontin,，OPN）是觸發(fā)疤痕形成的基因之一,。在傷口敷上一種能夠抑制OPN的膠體，可以加速愈合,，減少疤痕,。它的作用是增加傷口周圍的血管再生和加快組織重建。
該研究結(jié)果將發(fā)表在1月26日的Journal of Experimental Medicine上,。
Martin教授說,，白血細(xì)胞（巨噬細(xì)胞），運(yùn)送到傷口細(xì)胞的化學(xué)信號(hào),，以及骨橋蛋白本身都可做為靶標(biāo),，用于研制改善皮膚傷口愈合或其它纖維化組織修復(fù)的藥物。我們希望不久以后,，這種療法能夠用于臨床,。
Martin教授實(shí)驗(yàn)室和其他人之前的研究，包括人類在內(nèi)的許多物種的胚胎,，愈合傷口不留疤痕?，F(xiàn)在看來，在成年人中同樣的情況也可能屬實(shí),。
生物谷推薦原始出處：
Published online 7 January 2008
doi:10.1084/jem.20071412
The Journal of Experimental Medicine, Vol. 205, No. 1, 43-51
Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring
Ryoichi Mori1,2, Tanya J. Shaw1, and Paul Martin1,2
1 Departments of Physiology and 2 Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK
CORRESPONDENCE Paul Martin: [email protected]
Previous studies of tissue repair have revealed osteopontin (OPN) to be up-regulated in association with the wound inflammatory response. We hypothesize that OPN may contribute to inflammation-associated fibrosis. In a series of in vitro and in vivo studies, we analyze the effects of blocking OPN expression at the wound, and determine which inflammatory cells, and which paracrine factors from these cells, may be responsible for triggering OPN expression in wound fibroblasts. Delivery of OPN antisense oligodeoxynucleotides into mouse skin wounds by release from Pluronic gel decreases OPN protein levels at the wound and results in accelerated healing and reduced granulation tissue formation and scarring. To identify which leukocytic lineages may be responsible for OPN expression, we cultured fibroblasts in macrophage-, neutrophil-, or mast cell–conditioned media (CM), and found that macrophage- and mast cell–secreted factors, specifically platelet-derived growth factor (PDGF), induced fibroblast OPN expression. Correspondingly, Gleevec, which blocks PDGF receptor signaling, and PDGF-Rβ–neutralizing antibodies, inhibited OPN induction by macrophage-CM. These studies indicate that inflammation-triggered expression of OPN both hinders the rate of repair and contributes to wound fibrosis. Thus, OPN and PDGF are potential targets for therapeutic modulation of skin repair to improve healing rate and quality.
