Objective: Tissue kallikrein, a widely used vasodilator for the treatment of hypertension and peripheral circulatory disorder, acts by releasing kinin, a potent vasodilator peptide. To identify the role of tissue kallikrein in retinal neovascularization, we investigated the antiangiogenic effect by using an in vitro and in vivo angiogenesis model.
Methods And Results: Tissue kallikrein in vitreous fluid was markedly elevated in proliferative diabetic retinopathy patients compared with that in control patients with macular hole and epiretinal membrane. Tissue kallikrein inhibited vascular endothelial growth factor-165 (VEGF165)-induced tube formation, proliferation, and migration in vitro angiogenesis model via suppression of the VEGF165-induced phosphorylation of VEGF receptor-2. Furthermore, tissue kallikrein cleavage of VEGF165 was on the C-terminal side, which was analyzed by Western blotting and mass spectrometry. When administered subcutaneously, tissue kallikrein reduced the pathological vascular changes in retinal neovascularization induced in neonatal mice by returning the retina to normoxia after exposure to hyperoxia.
Conclusions: These findings indicate that tissue kallikrein is partly involved in pathogenesis of proliferative diabetic retinopathy and may be a promising therapeutic agent that could cleave VEGF165 itself when administered by a peripheral route.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/ATVBAHA.111.223594 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Probing the familial ties between serpin members Kallistatin and PEDF: A comparative analysis review.
Life Sci
December 2024
Department of Biochemistry and Molecular Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China; China Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou 510080, China; Guangdong Province Key Laboratory of Diabetology, Guangzhou 510080, China. Electronic address:
The serine protease inhibitors (Serpins) represent a diverse protein superfamily that holds paramount significance in governing vital pathophysiological processes. Their influence on critical biological pathways renders serpins highly coveted targets for drug discovery endeavors. Among the numerous members of this family, two distinct proteins, Kallistatin (encoded by the SERPINA4 gene) and Pigment Epithelium-Derived Factor (PEDF, encoded by the SERPINF1 gene), stand out as secreted proteins that are abundantly present in peripheral blood.
View Article and Find Full Text PDFDeficiency of neutrophil gelatinase-associated lipocalin elicits Hemophilia-like bleeding and clotting disorder.
Blood
December 2024
School of Basic Medicine, Qingdao University, Qingdao, China.
Coagulation is related to inflammation, but the key pathway, especially innate immune system and coagulation regulation, is not well understood and need to be further explored. Here, we demonstrated that neutrophil gelatinase-associated lipocalin (NGAL), an innate immune inflammatory mediator, is upregulated in thrombosis patients. Furthermore, it contributes to the initiation and amplification of coagulation, hemostasis, and thrombosis.
View Article and Find Full Text PDFActivation of Bradykinin B Receptors in Astrocytes Stimulates the Release of Leukemia Inhibitory Factor for Autocrine and Paracrine Signaling.
Int J Mol Sci
December 2024
Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Communications between different cell types within a tissue are often critical for the proper functioning of an organ. In the central nervous system, interactions among neurons and glial cells are known to modulate neurotransmission, energy metabolism, extracellular ion homeostasis, and neuroprotection. Here we showed that bradykinin, a proinflammatory neuropeptide, can be detected by astrocytes, resulting in the secretion of cytokines that act on neurons.
View Article and Find Full Text PDFAnalysis of kallikrein-related peptidase 7 (KLK7) autolysis reveals novel protease and cytokine substrates.
Biol Chem
December 2024
Departments of Biological Chemistry and Early Discovery Biochemistry, Genentech Inc., South San Francisco, CA, 94080, USA.
Kallikrein-related peptidase 7 (KLK7) is one of 15 members of the tissue kallikrein family and is primarily expressed in the skin epidermis. The activity of KLK7 is tightly regulated by multiple stages of maturation and reversible inhibition, similar to several other extracellular proteases. In this work, we used protease-specific inhibitors and active site variants to show that KLK7 undergoes autolysis at two separate sites in the 170 and 99 loops (chymotrypsinogen numbering), resulting in a loss of enzymatic activity.
View Article and Find Full Text PDFThe potential immunotherapy effect of Ginkgolide B thwarts oral squamous cell carcinoma progression by targeting the SREBP1/KLK8/CCL22 axis.
Phytomedicine
November 2024
Department of Molecular Biology and Cell Research, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan; Department of Hematology‑Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan.
Background: Oral cancer is a malignant tumor of the oral cavity, with regulatory T cell (Treg) infiltration associated with poor prognosis. Ginkgolide B (GB) has demonstrated effects on lipid metabolism; however, its potential immunotherapeutic effects on oral cancer have not been elaborated.
Purpose: This study aimed to explore the immunotherapeutic effects of Ginkgolide B (GB) in oral cancer.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!