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

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 (BTPs) 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 have investigated a possible role for PCPE-1 in corneal scarring. Although differences in corneal opacity associated with scarring following injury of Pcolce−/− and 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.

Elevated serum levels of procollagen C‐proteinase enhancer‐1 in patients with chronic kidney disease is associated with a declining glomerular filtration rate

“…16 Recent studies have also shown that PCPE-1 is associated with corneal scarring and dermal scar formation. 17,18 Our review of the literature revealed no studies reporting the relationship between CKD and PCPE-1. PCPE-1 levels in patients with CKD in our study were significantly higher than in the healthy controls.…”

“…Kessler‐Icekson et al showed an association between PCPE‐1 and aldosterone‐mediated fibrosis in heart tissue during remodelling following acute myocardial infarction in rats . Recent studies have also shown that PCPE‐1 is associated with corneal scarring and dermal scar formation . Our review of the literature revealed no studies reporting the relationship between CKD and PCPE‐1.…”

Procollagen C-Proteinase Enhancer 1 (PCPE-1) is a marker of myocardial fibrosis and impaired cardiac function in a murine model of pressure overload

“…The link between PCPE-1 up-regulation and fibrosis has already been demonstrated in several organs such as liver, muscle, skin or cornea [25][26][27][28] . Regarding cardiac fibrosis, PCPE-1 was found to be increased in endomyocardial biopsies from a cohort of 28 patients suffering from aortic valve stenosis 29 .…”

Up-regulation of PCOLCE by TWIST1 promotes metastasis in Osteosarcoma

“…For instance, the expression of PCOLCE positively correlates with muscle and liver fibrosis 16. A PCOLCE deficiency contributes to deficient corneal repair 17. Mutated PABPN1 binds to PCOLCE and entraps it within the nuclear compartment, leading to oculopharyngeal muscular dystrophy 18.…”