Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
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Anne Pizard
Abstract
Tissue kallikrein (KLK1) is a kinin-forming serine protease synthesized in many organs including arteries and kidney. Study of the physiological role of KLK1 has benefited from the availability of mouse and human genetic models of KLK1 deficiency, through engineering of KLK1 mouse mutants and discovery of a major polymorphism in the human KLK1 gene that induces a loss of enzyme activity. Studies in KLK1-deficient mice and human subjects partially deficient in KLK1 have documented its critical role in arterial function in both species. KLK1 is also involved in the control of ionic transport in the renal tubule, an action that may not be kinin-mediated. Studies of experimental diseases in KLK1-deficient mice have revealed cardio- and nephro-protective effects of KLK1 and kinins in acute cardiac ischemia, post-ischemic heart failure, and diabetes. Potential clinical and therapeutic developments are discussed.
©2008 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Editorial
- Kallikreins and kallikrein-related peptidases
- Guest Editorial
- The 2nd International Symposium on Kallikreins and Kallikrein-Related Peptidases (ISK 2007) and the Commemorative Gold Medal of the E.K. Frey–E. Werle Foundation of the Henning L. Voigt Family
- Highlight: Kallikrein, kinins and kallikrein-related peptidases
- Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
- Development of peptides specifically modulating the activity of KLK2 and KLK3
- Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
- Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)
- Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions
- A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology
- microRNAs: a new frontier in kallikrein research
- Functions of KLK4 and MMP-20 in dental enamel formation
- Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
- Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling
- Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
- Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model
- Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia
- Kallikreins as microRNA targets: an in silico and experimental-based analysis
- Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration
- Immunofluorometric activity-based probe analysis of active KLK6 in biological fluids
- Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
- Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
- An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines
- Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung
Artikel in diesem Heft
- Editorial
- Kallikreins and kallikrein-related peptidases
- Guest Editorial
- The 2nd International Symposium on Kallikreins and Kallikrein-Related Peptidases (ISK 2007) and the Commemorative Gold Medal of the E.K. Frey–E. Werle Foundation of the Henning L. Voigt Family
- Highlight: Kallikrein, kinins and kallikrein-related peptidases
- Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
- Development of peptides specifically modulating the activity of KLK2 and KLK3
- Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
- Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)
- Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions
- A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology
- microRNAs: a new frontier in kallikrein research
- Functions of KLK4 and MMP-20 in dental enamel formation
- Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
- Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling
- Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
- Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model
- Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia
- Kallikreins as microRNA targets: an in silico and experimental-based analysis
- Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration
- Immunofluorometric activity-based probe analysis of active KLK6 in biological fluids
- Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
- Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
- An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines
- Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung