A guide to murine fibrinolytic factor structure, function, assays, and genetic alterations

Matsuo, Osamu; Lijnen, H.R.; Ueshima, Shigeru; Kojima, Soichi; Smyth, Susan S.

doi:10.1111/j.1538-7836.2007.02409.x

Cited by 15 publications

(9 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In summary, Plg-R KT À/À mice mimic some, but not all, spontaneous phenotypes exhibited by Plg À/À mice [29], consistent with a role for this plasminogen receptor in specific physiological and pathological functions. Notably, although Plg-R KT deficiency was compatible with survival of individual mice, Plg-R KT deficiency is not compatible with survival of the species due to the death of all offspring of Plg-R KT À/À females.…”

Section: Plg-r Kt Null Macrophages Exhibit a Marked Deficiency In Plasupporting

confidence: 56%

Deficiency of plasminogen receptor, Plg‐RKT, causes defects in plasminogen binding and inflammatory macrophage recruitment in vivo

Miles

Baik

Lighvani

et al. 2017

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Summary Background Plg-RKT is a novel integral membrane plasminogen receptor that binds plasminogen via a C-terminal lysine exposed on the cell surface and promotes plasminogen activation on the cell surface by both tissue plasminogen activator and urokinase plasminogen activator. Objectives To evaluate the role of Plg-RKT in vivo we generated Plg-RKT-/- mice using a homologous recombination technique. Methods We characterized the effect of Plg-RKT deletion on reproduction, viability, health, and spontaneous thrombosis and inflammation. Results Plg-RKT-/- mice were viable and fertile. Survival of Plg-RKT-/- mice and Plg-RKT+/+ littermates was not significantly different. However, quite strikingly, all pups of Plg-RKT-/- females died within 2 days of birth, consistent with a lactation defect in Plg-RKT-/- mothers. Additionally, there was a significant effect of Plg-RKT deficiency on growth rates of female, but not male mice. In experimental peritonitis studies, Plg-RKT-/- mice exhibited a marked defect in macrophage recruitment. As a contributing mechanism, the capacity of Plg-RKT-/- macrophages for plasminogen binding was markedly decreased. Conclusions These studies demonstrate that Plg-RKT is required for plasminogen binding and macrophage migration in vivo. In addition, Plg-RKT deficiency is not compatible with survival of the species, due to death of all offspring of Plg-RKT-/- females. This new mouse model will be important for future studies aimed at delineating the role of cell surface plasminogen activation in challenge and disease models in vivo.

show abstract

Section: Plg-r Kt Null Macrophages Exhibit a Marked Deficiency In Plasupporting

confidence: 56%

Deficiency of plasminogen receptor, Plg‐RKT, causes defects in plasminogen binding and inflammatory macrophage recruitment in vivo

Miles

Baik

Lighvani

et al. 2017

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…In the remodeling phase, bone formation and resorption are tightly regulated by osteoblasts and osteoclasts . Plasminogen is a pivotal component of the tissue fibrinolytic system, and plasmin plays crucial roles in the activation of the tissue proteolytic system and the release of growth factors, including TGF‐β and VEGF, from the ECM . Previous studies indicate that plasminogen is important for tissue repair in the skin and liver beyond the degradation of fibrin .…”

Section: Discussionmentioning

confidence: 99%

“…(5) Plasminogen, a pivotal component of the fibrinolytic system, is an inactive proenzyme that is converted to the active serine protease plasmin by tissue-type plasminogen activator (t-PA) and urokinase-type PA (u-PA). (6) The fibrinolytic system has many physiological and pathophysiological functions in mammals beyond its proteolytic effect on thrombi. Plasmin activates the tissue proteolytic system.…”

Section: Introductionmentioning

confidence: 99%

Plasminogen Plays a Crucial Role in Bone Repair

Kawao

Tamura

Okumoto

et al. 2013

Journal of Bone and Mineral Research

105

View full text Add to dashboard Cite

The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver. However, the role of the fibrinolytic system in bone regeneration remains unknown. Herein, we investigated bone repair and ectopic bone formation using plasminogen-deficient (Plg -/-) mice. Bone repair of the femur is delayed in Plg -/-mice, unlike that in the wild-type (Plg þ/þ ) mice. The deposition of cartilage matrix and osteoblast formation were both decreased in Plg -/-mice. Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor (VEGF) and transforming growth factor-b (TGF-b) were decreased at the site of bone damage in Plg -/-mice. Conversely, heterotopic ossification was not significantly different between Plg þ/þ and Plg -/-mice. Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF-b were comparable between Plg þ/þ and Plg -/-mice in heterotopic ossification. Our data provide novel evidence that plasminogen is essential for bone repair. The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF-b, and VEGF, thereby leading to the enhancement of bone repair.

show abstract

“…136 It needs to be stated that in addition to multiple informative parallels, multiple divergences exist between humans and mice in regards to hemostatic and thrombotic processes, as do differences between strains of mice, and these must be considered in experimental design. Comprehensive considerations of comparative mouse and human hemostasis are available 137; 138; 139 and strain specific differences in normal ranges for coagulation assays are available in the Mouse Phenome Database (available at: http://phenome.jax.ohrg/pub-cgi/phenome/mpdcgi?rtn=meas/catlister&req=Cblood%20hematologyqqqcoagulation). …”

Section: The Hemophilia B Mouse Modelmentioning

confidence: 99%

Animal Models of Hemophilia

Sabatino

Nichols

Merricks

et al. 2012

Progress in Molecular Biology and Translational Science

View full text Add to dashboard Cite

The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes.

show abstract

A guide to murine fibrinolytic factor structure, function, assays, and genetic alterations

Cited by 15 publications

References 100 publications

Deficiency of plasminogen receptor, Plg‐RKT, causes defects in plasminogen binding and inflammatory macrophage recruitment in vivo

Deficiency of plasminogen receptor, Plg‐RKT, causes defects in plasminogen binding and inflammatory macrophage recruitment in vivo

Plasminogen Plays a Crucial Role in Bone Repair

Animal Models of Hemophilia

Contact Info

Product

Resources

About