ArticleDiabetologia2003
Kallikrein-binding protein inhibits retinal neovascularization and decreases vascular leakage.
Article in Diabetologia, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 64 citations in OpenAlex.
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- Protective Role of Kallistatin in Vascular and Organ Injury.Hypertension (Dallas, Tex. : 1979) · 2016Review
- The Potential Role of Kallistatin in the Development of Abdominal Aortic Aneurysm.International journal of molecular sciences · 2016Review
- Ras-related C3 botulinum toxin substrate 1 activation is involved in the pathogenesis of diabetic retinopathy.Experimental and therapeutic medicine · 2015Article
- Kallistatin modulates immune cells and confers anti-inflammatory response to protect mice from group A streptococcal infection.Antimicrobial agents and chemotherapy · 2013Article
- Thyroid hormone and COUP-TF1 regulate kallikrein-binding protein (KBP) gene expression.Endocrinology · 2011Article
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- The potential of nanomedicine therapies to treat neovascular disease in the retina.Journal of angiogenesis research · 2010Article
- Wnt pathway antagonists and angiogenesis.Protein & cell · 2010Review
- Plasma kallikrein and diabetic macular edema.Current diabetes reports · 2010Article
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- Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models.The American journal of pathology · 2009Article
- Pigment epithelium-derived factor suppresses adipogenesis via inhibition of the MAPK/ERK pathway in 3T3-L1 preadipocytes.American journal of physiology. Endocrinology and metabolism · 2009Article
- SERPINA3K prevents oxidative stress induced necrotic cell death by inhibiting calcium overload.PloS one · 2008Article
- Kallikrein-kinin activation by altered vitreous pH: New perspectives for treatment and pathogenesis of diabetic macular edema? : Comment on: Gao BB et al. Extracellular carbonic anhydrase mediates hemorrhagic retinal and cerebral vascular permeability through prekallikrein activation. Nat Med. 2007 Feb;13(2):181-8.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2007Article
- Up-regulation of integrin-linked kinase in the streptozotocin-induced diabetic rat retina.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2007Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisKallikrein-binding protein (KBP) is a serine proteinase inhibitor (serpin). It specifically binds to tissue kallikrein and inhibits kallikrein activity. Our study was designed to test its effects on retinal neovascularization and vascular permeability.
methodsEndothelial cell proliferation was determined by [(3)H] thymidine incorporation assay and apoptosis quantified by Annexin V staining and flow cytometry. Effect on retinal neovascularization was determined by fluorescein angiography and count of pre-retinal vascular cells in an oxygen-induced retinopathy (OIR) model. Vascular permeability was assayed by the Evans blue method. Vascular endothelial growth factor (VEGF) was measured by Western blot analysis and ELISA.
resultsKallikrein-binding protein specifically inhibited proliferation and induced apoptosis in retinal capillary endothelial cells. Intravitreal injection of KBP inhibited retinal neovascularization in an OIR model. Moreover, KBP decreased vascular leakage in the retina, iris and choroid in rats with OIR. Blockade of kinin receptors by specific antagonists showed significantly weaker inhibition of endothelial cells, when compared to that of KBP, suggesting that the anti-angiogenic activity of KBP is not through inhibiting kallikrein activity or kinin production. KBP competed with (125)I-VEGF for binding to endothelial cells and down-regulated VEGF production in endothelial cells and in the retina of the OIR rat model. CONCLUSION/
interpretationKallikrein-binding protein is a multi-functional serpin, and its vascular activities are independent of its interactions with the kallikrein-kinin system. Inhibition of VEGF binding to its receptors and down-regulation of VEGF expression could represent a mechanism for the vascular activities of KBP.
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