Transcriptional Profiling of Rapamycin-Treated Fibroblasts From Hypertrophic and Keloid Scars

Wong, Victor W.; You, Fanglei; Januszyk, Michael; Gurtner, Geoffrey C.; Kuang, Anna A.

doi:10.1097/sap.0b013e31826956f6

Cited by 40 publications

(32 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with a role in collagen biosynthetic maturation, increased PCPE-1 expression is reported to accompany fibrosis onset in animal models of hepatic cirrhosis (Hassoun, et al, 2016, Ippolito, et al, 2016, Ogata, et al, 1997), cardiac fibrosis (Kessler-Icekson, et al, 2006, Yu, et al, 2013), and skeletal muscle fibrosis (Hassoun, et al, 2016); and in human dermal scarring (Wong, et al, 2014). Differences in PCPE-1 expression levels in quiescent versus proliferating smooth muscle cells (Kanaki, et al, 2000), and the induced anchorage-independent growth of cultured fibroblasts in which the PCPE-1 gene has been disrupted (Masuda, et al, 1998), have also suggested a possible role for PCPE-1 in cell proliferation control.…”

Section: Introductionmentioning

confidence: 62%

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 62%

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

et al. 2017

View full text Add to dashboard Cite

show abstract

“…For example, injection of a small molecule inhibitor of BTPs reduced scar elevation in a rabbit skin model of hypertrophic scarring [91], presumably by reducing collagen deposition following wounding. Consistent with this, transcription of PCPE-1 was recently found to be up-regulated in samples of hypertrophic and keloid scars [92], as was expression of both BMP-1 and PCPE-1 in a mouse model of corneal scarring [93]. Following the discovery that mTLD was present in human plasma, increasing the amount of circulating mTLD in a rat model of chronic kidney disease was found to exacerbate renal fibrosis, while the opposite effect followed treatment with an anti-mTLD antibody [82].…”

Section: New Targets For Therapy Fibrosismentioning

confidence: 70%

BMP-1/tolloid-like proteinases synchronize matrix assembly with growth factor activation to promote morphogenesis and tissue remodeling

2015

View full text Add to dashboard Cite

Bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases, here called BTPs, include the proteases originally identified for their roles in the C-terminal maturation of fibrillar procollagens ("procollagen C-proteinase"). Though numerous other substrates have since been discovered, the BTPs remain the main proteases involved in extracellular matrix assembly with little or no implication in matrix degradation. During the same period however, the BTPs have also become established as important proteases in the activation of growth factors, including TGF-β1, BMP-2/-4, GDF-8/-11 and IGFs, as well as the release of anti-angiogenic fragments from parent proteins. The BTPs are therefore key players in many pathophysiological processes such as morphogenesis, tissue repair and tumor progression. This mini-review summarizes our current knowledge of the functions of BTPs, their substrates and unusual mechanisms of regulation, and discusses their potential as new targets for future therapies.

show abstract

“…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.…”

Section: Discussionmentioning

confidence: 93%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

View full text Add to dashboard Cite

Background Procollagen C‐proteinase enhancer‐1 (PCPE‐1) is a 55 kDa glycoprotein, which increases the activity of procollagen C‐proteinases that break down C‐terminal propeptides. Studies have shown that PCPE‐1 is involved in the fibrotic process that occurs in various tissues and organs. Our review of the literature revealed no data concerning the relation between PCPE‐1 and chronic kidney disease (CKD). The purpose of this study was to determine PCPE‐1 levels in CKD. Methods One hundred thirty‐one CKD patients and 34 healthy controls were included in our study. Demographic data were recorded, and routine biochemical tests were performed. Blood specimens were collected for PCPE‐1 investigation. Demographic data, biochemical test results and PCPE‐1 levels were compared between the control and patient groups. Parameters affecting PCPE‐1 levels in our patient group were assessed. Results Procollagen C‐proteinase enhancer‐1 levels were significantly higher in our patient group compared to the control group. Parameters affecting PCPE‐1 elevation in the patient group were identified as systolic blood pressure, blood urea nitrogen, phosphorus, haemoglobin, intact parathormone levels, glomerular filtration rate and body mass index. Conclusion We determined high PCPE‐1 levels in CKD patients. PCPE‐1 levels being negatively correlated with glomerular filtration rate suggests that PCPE‐1 may be associated with progression in CKD patients.

show abstract

Transcriptional Profiling of Rapamycin-Treated Fibroblasts From Hypertrophic and Keloid Scars

Cited by 40 publications

References 53 publications

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

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

BMP-1/tolloid-like proteinases synchronize matrix assembly with growth factor activation to promote morphogenesis and tissue remodeling

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

Contact Info

Product

Resources

About