High-molecular weight kininogen. A secreted platelet protein.

Schmaier, Alvin H.; Zuckerberg, A; Silverman, Carol; Kuchibhotla, Jaya; Tuszynski, George P.; Colman, Robert W.

doi:10.1172/jci110901

Cited by 110 publications

(58 citation statements)

References 49 publications

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“…One unit was defined as that amount of procoagulant activity in I ml ofpooled normal plasma. HMWK antigen was measured by a competitive ELISA, performed as previously reported (12) using a monospecific polyclonal antibody directed to the 56-kD light chain of HMWK (12). HNE activity was measured by a chromogenic assay using the substrate, methoxysuccinyl-Ala-Ala-Pro-Val-pNA (24) and antigenic levels were measured using a competitive ELISA specific for HNE (8).…”

Section: Methodsmentioning

confidence: 99%

“…We postulated that kallikrein might bind to neutrophils through its cofactor, HMWK, with which it complexes. Platelets have been shown to contain a form of HMWK (12,13), which can be expressed on the activated platelet surface (14). As HMWK has been shown to bind to activated (15) and unstimulated (16) platelets, studies were initiated to determine if neutrophils also contain a form' of HMWK and whether the external membrane of human neutrophils possesses a specific binding site for HMWK.…”

Section: Introductionmentioning

confidence: 99%

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Human neutrophils contain and bind high molecular weight kininogen.

Gustafson¹,

Wachtfogel²,

Kaufman³

et al. 1989

J. Clin. Invest.

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101

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human neutrophils contain and bind high molecular weight kininogen.

Gustafson¹,

Wachtfogel²,

Kaufman³

et al. 1989

J. Clin. Invest.

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101

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“…Coupled (top) and uncoupled (bottom) band density ratios were determined using densitometry (Scion Image). 18 Ratios were standardized to the average WT ratio values of RIPA-buffer homogenized samples.…”

Section: Determination Of Uncoupled Enosmentioning

confidence: 99%

Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis

Adams¹,

LaRusch²,

Stavrou³

et al. 2011

Blood

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“…Human kininogens are multi-domain plasma proteins that are primarily synthesized in the liver (1,2). Both high molecular weight and low molecular weight kininogens are transcribed from a single gene via alternative splicing (3,4).…”

mentioning

confidence: 99%

“…Both high molecular weight and low molecular weight kininogens are transcribed from a single gene via alternative splicing (3,4). Human high molecular weight kininogen (HK) 1 serves as a cofactor for activation of prekallikrein and Factor XI (5,6). Activated prekallikrein cleaves HK, producing the two-chain kinin-free kininogen (HKa) and sequentially releasing the short-lived vasoactive agent bradykinin (7,8).…”

mentioning

confidence: 99%

Human Kininogen Gene Is Transactivated by the Farnesoid X Receptor

Zhao

Lew

Huang

et al. 2003

Journal of Biological Chemistry

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Human kininogen belongs to the plasma kallikreinkinin system. High molecular weight kininogen is the precursor for two-chain kinin-free kininogen and bradykinin. It has been shown that the two-chain kinin-free kininogen has the properties of anti-adhesion, antiplatelet aggregation, and anti-thrombosis, whereas bradykinin is a potent vasodilator and mediator of inflammation. In this study we show that the human kininogen gene is strongly up-regulated by agonists of the farnesoid X receptor (FXR), a nuclear receptor for bile acids. In primary human hepatocytes, both the endogenous FXR agonist chenodeoxycholate and synthetic FXR agonist GW4064 increased kininogen mRNA with a maximum induction of 8 -10-fold. A more robust induction of kininogen expression was observed in HepG2 cells, where kininogen mRNA was increased by chenodeoxycholate or GW4064 up to 130 -140-fold as shown by real time PCR. Northern blot analysis confirmed the up-regulation of kininogen expression by FXR agonists. To determine whether kininogen is a direct target of FXR, we examined the sequence of the kininogen promoter and identified a highly conserved FXR response element (inverted repeat, IR-1) in the proximity of the kininogen promoter (؊66/؊54). FXR/RXR␣ heterodimers specifically bind to this IR-1. A construct of a minimal promoter with the luciferase reporter containing this IR-1 was transactivated by FXR. Deletion or mutation of this IR-1 abolished FXR-mediated promoter activation, indicating that this IR-1 element is responsible for the promoter transactivation by FXR. We conclude that kininogen is a novel and direct target of FXR, and bile acids may play a role in the vasodilation and anti-coagulation processes.

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High-molecular weight kininogen. A secreted platelet protein.

Cited by 110 publications

References 49 publications

Human neutrophils contain and bind high molecular weight kininogen.

Human neutrophils contain and bind high molecular weight kininogen.

Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis

Human Kininogen Gene Is Transactivated by the Farnesoid X Receptor

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