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原胶原蛋白 C-蛋白酶增强子 1(PCPE-1)作为一种抗血管生成因子,可增强受损角膜的上皮修复。

Procollagen C-proteinase enhancer 1 (PCPE-1) functions as an anti-angiogenic factor and enhances epithelial recovery in injured cornea.

机构信息

Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, 4503 WIMRII, 1111 Highland Ave., Madison, WI, 53705, USA.

出版信息

Cell Tissue Res. 2017 Dec;370(3):461-476. doi: 10.1007/s00441-017-2689-6. Epub 2017 Sep 21.

Abstract

Procollagen C-proteinase enhancer 1 (PCPE-1) has been characterized as a protein capable of enhancing the activity of bone morphogenetic protein 1/tolloid-like proteinases in the biosynthetic processing of C-propeptides from procollagens I-III. This processing step is thought necessary to the formation of collagen I-III monomers capable of forming fibrils. Thus, PCPE-1 is predicted to play an important role in scarring, as scar tissue is predominantly composed of fibrillar collagen. Corneal scarring is of great clinical importance, as it leads to loss of visual acuity and, in severe cases, blindness. Here, we investigate a possible role for PCPE-1 in corneal scarring. Although differences in corneal opacity associated with scarring following injury of Pcolce and wild-type (WT) mice using full-thickness excision or alkali burn models of corneal injury were not grossly apparent, differences in procollagen I processing levels between Pcolce and WT primary corneal keratocytes were consistent with a role for PCPE-1 in corneal collagen deposition. An unexpected finding was that neoangiogenesis, which follows alkali burn cornea injury, was strikingly increased in Pcolce cornea, compared to WT. A series of aortic ring assays confirmed the anti-angiogenic effects of PCPE-1. Another unexpected finding was of abnormalities of epithelial basement membrane and of re-epithelialization following Pcolce corneal injury. Thus, PCPE-1 appears to be of importance as an anti-angiogenic factor and in re-epithelialization following injury in cornea and perhaps in other tissues as well.

摘要

原胶原蛋白 C 蛋白酶增强子 1(PCPE-1)已被鉴定为一种能够增强骨形态发生蛋白 1/类金属蛋白酶的活性的蛋白质,该酶在原胶原蛋白 I-III 的 C 端前肽的生物合成加工中起作用。该加工步骤被认为是形成能够形成纤维的 I-III 型胶原单体所必需的。因此,PCPE-1 预计在瘢痕形成中发挥重要作用,因为瘢痕组织主要由纤维状胶原组成。角膜瘢痕形成具有重要的临床意义,因为它会导致视力丧失,在严重的情况下会导致失明。在这里,我们研究了 PCPE-1 在角膜瘢痕形成中的可能作用。尽管在用全层切除术或碱烧伤模型损伤 Pcolce 和野生型(WT)小鼠后,与瘢痕相关的角膜混浊程度没有明显差异,但 Pcolce 和 WT 原代角膜成纤维细胞之间原胶原蛋白 I 加工水平的差异与 PCPE-1 在角膜胶原沉积中的作用一致。一个意外的发现是,与 WT 相比,在 Pcolce 角膜中,碱烧伤角膜损伤后新生血管形成显著增加。一系列主动脉环测定证实了 PCPE-1 的抗血管生成作用。另一个意外的发现是 Pcolce 角膜损伤后上皮基底膜和再上皮化的异常。因此,PCPE-1 似乎在角膜和其他组织的损伤后作为抗血管生成因子和再上皮化中具有重要作用。

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