ArticleThe Journal of clinical investigation1999
A potential role for protease nexin 1 overexpression in the pathogenesis of scleroderma.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 39 citations in OpenAlex.
- Protease nexin-1 deficiency increases mouse hindlimb neovascularisation following ischemia and accelerates femoral artery perfusion.Scientific reports · 2021Article
- Machine learning integration of scleroderma histology and gene expression identifies fibroblast polarisation as a hallmark of clinical severity and improvement.Annals of the rheumatic diseases · 2021Article
- Protease Nexin-1 in the Cardiovascular System: Wherefore Art Thou?Frontiers in cardiovascular medicine · 2021Review
- Increased expression of protease nexin-1 in fibroblasts during idiopathic pulmonary fibrosis regulates thrombin activity and fibronectin expression.Laboratory investigation; a journal of technical methods and pathology · 2014Article
- Serum levels of soluble CD21 in patients with systemic sclerosis.Rheumatology international · 2012Article
- Serine proteases, inhibitors and receptors in renal fibrosis.Thrombosis and haemostasis · 2009Review
- Persistent down-regulation of Fli1, a suppressor of collagen transcription, in fibrotic scleroderma skin.The American journal of pathology · 2003Article
- Ligand-dependent genetic recombination in fibroblasts : a potentially powerful technique for investigating gene function in fibrosis.The American journal of pathology · 2002Article
- Glomerulosclerosis is transmitted by bone marrow-derived mesangial cell progenitors.The Journal of clinical investigation · 2001Article
- The promise of transcription profiling for understanding the pathogenesis of scleroderma.Current rheumatology reports · 2000Review
- Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Fibroblast heterogeneity in physiological conditions and fibrotic disease.Springer seminars in immunopathology · 1999Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Scleroderma currently affects approximately 75,000-100,000 individuals in the United States. Fibroblasts isolated from lesional skin of scleroderma patients overexpress collagens and other matrix components, and this abnormality is maintained for multiple passages in culture. To understand the molecular basis for matrix gene overexpression, we performed a differential display comparison of fibroblasts from clinically lesional and nonlesional scleroderma skin. The results suggested that protease nexin 1 (PN1), a protease inhibitor, is overexpressed in scleroderma fibroblasts. Northern blot verification showed that lesional and nonlesional scleroderma fibroblasts had three- to five-fold increased levels of PN1 mRNA compared with healthy fibroblasts. Western analysis showed that scleroderma fibroblasts also secreted more PN1. In situ hybridization of skin biopsy specimens demonstrated PN1 expression in the dermis of four out of six scleroderma patients but no PN1 expression in the dermis of six healthy volunteers. Transient or stable overexpression of PN1 in mouse 3T3 fibroblasts increased collagen promoter activity or endogenous collagen transcript levels, respectively. PN1 mutagenized at its active site and antisense PN1 both failed to increase collagen promoter activity. These results suggest that overexpression of enzymatically active PN1 may play a pathogenic role in the development of the scleroderma phenotype.
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Registered trials
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