Tissue factor and thrombomodulin expression on keratinocytes as coagulation/anti‐coagulation cofactor and differentiation marker

Mizutani, Hitoshi; Ohyanagi, Satoshi; Nouchi, Nobuyuki; Inachi, Shin; Shimizu, Masayuki

doi:10.1111/j.1440-0960.1996.tb01085.x

Cited by 6 publications

(2 citation statements)

References 4 publications

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“…Therefore, we centered our focus on the investigation of direct FVIIa signaling in wound healing. Of note, TF is expressed in keratinocytes under physiological conditions (46), suggesting an environment in which FVIIa/TF signaling might be functioning. Indeed, a previous study showed that stimulating a human HaCa-T keratinocyte cell line with FVIIa induced gene transcripts with a pattern very similar to those found in a woundtype response (26).…”

Section: Discussionmentioning

confidence: 99%

Factor VII Deficiency Impairs Cutaneous Wound Healing in Mice

Ploplis

et al. 2010

Mol Med

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Skin keratinocytes express tissue factor (TF) and are highly associated with skin wound healing. Although it has been demonstrated that perivascular TF expression in granulation tissue formed after dermal injury is downregulated during healing, studies of the mechanism of factor (F) VII, a TF ligand, in skin wound healing are lacking. We reported the use of a dermal punch model to demonstrate that low-expressing FVII mice (~1% of wild type [WT]) exhibited impaired skin wound healing compared with WT controls. These low-FVII mice showed defective reepithelialization and reduced inflammatory cell infiltration at wound sites. This attenuated reepithelialization was associated with diminished expression of the transcription factor early growth response 1 (Egr-1). In vitro, Egr-1 was shown to be essential for the FVIIa-induced regulation of keratinocyte migration and inflammation. Both Egr-1 upregulation and downstream inflammatory cytokine appearance in keratinocytes depended on FVIIa/TF/protease-activated receptor 2 (PAR-2)-induced signaling and did not require subsequent generation of FXa and thrombin. The participation of Egr-1 in FVIIa-mediated regulation of keratinocyte function was confirmed by use of Egr-1-deficient mice, wherein a significant delay in skin wound healing after injury was observed, relative to WT mice. The results from these studies demonstrate an in vivo mechanistic relationship between FVIIa, Egr-1 and the inflammatory response in keratinocyte function during the wound healing process.

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Section: Discussionmentioning

confidence: 99%

Factor VII Deficiency Impairs Cutaneous Wound Healing in Mice

Ploplis

et al. 2010

Mol Med

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“…The activation of both the intrinsic and extrinsic pathways of blood coagulation by PF has been examined. The expression of tissue factor and thrombomodulin on keratinocytes shielding with PF were found to be upregulated, indicating the activation of coagulation and sign of ongoing thrombosis [176]. The association of PF with HK levels and plasma kallikrein levels has been examined [177].…”

Section: Role Of the Plasma Kks In Cardiovascular Abnormalitiesmentioning

confidence: 99%

Human Plasma Kallikrein-Kinin System: Physiological and Biochemical Parameters

Bryant

Shariat‐Madar²

2009

CHAMC

118

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The plasma kallikrein-kinin system (KKS) plays a critical role in human physiology. The KKS encompasses coagulation factor XII (FXII), the complex of prekallikrein (PK) and high molecular weight kininogen (HK). The conversion of plasma to kallikrein by the activated FXII and in response to numerous different stimuli leads to the generation of bradykinin (BK) and activated HK (HKa, an antiangiogenic peptide). BK is a proinflammatory peptide, a pain mediator and potent vasodilator, leading to robust accumulation of fluid in the interstitium. Systemic production of BK, HKa with the interplay between BK bound-BK receptors and the soluble form of HKa are key to angiogenesis and hemodynamics. KKS has been implicated in the pathogenesis of inflammation, hypertension, endotoxemia, and coagulopathy. In all these cases increased BK levels is the hallmark. In some cases, the persistent production of BK due to the deficiency of the blood protein C1-inhibitor, which controls FXII, is detrimental to the survival of the patients with hereditary angioedema (HAE). In others, the inability of angiotensin converting enzyme (ACE) to degrade BK leads to elevated BK levels and edema in patients on ACE inhibitors. Thus, the mechanisms that interfere with BK liberation or degradation would lead to blood pressure dysfunction. In contrast, anti-kallikrein treatment could have adverse effects in hemodynamic changes induced by vasoconstrictor agents. Genetic models of kallikrein deficiency are needed to evaluate the quantitative role of kallikrein and to validate whether strategies designed to activate or inhibit kallikrein may be important for regulating whole-body BK sensitivity.

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