Gene Symbol: Serpinf2
Description: serine (or cysteine) peptidase inhibitor, clade F, member 2
Alias: AI747498, Pli, Serpimf2, alpha-2-antiplasmin, alpha-2-AP, alpha-2-PI, alpha-2-plasmin inhibitor, pigment epithelium derived factor, plasmin inhibitor alpha 2, serine (or cysteine) proteinase inhibitor, clade F, member 2, serpin F2
Species: mouse
Products:     Serpinf2

Top Publications

  1. Hou Y, Okada K, Okamoto C, Ueshima S, Matsuo O. Alpha2-antiplasmin is a critical regulator of angiotensin II-mediated vascular remodeling. Arterioscler Thromb Vasc Biol. 2008;28:1257-62 pubmed publisher
    ..The results show that alpha2-AP is a critical regulator for vascular remodeling by inhibiting p53/p21 pathway, suggesting that alpha2-AP is proposed to be a potential therapeutic target for vascular remodeling. ..
  2. Kanno Y, Kuroki A, Okada K, Tomogane K, Ueshima S, Matsuo O, et al. Alpha2-antiplasmin is involved in the production of transforming growth factor beta1 and fibrosis. J Thromb Haemost. 2007;5:2266-73 pubmed
    ..This is the first report to describe the crucial role that alpha2AP plays in TGF-beta(1) synthesis during the process of fibrosis. Our results provide new insights into the role of alpha2AP in fibrosis. ..
  3. Kanno Y, Kawashita E, Minamida M, Kaneiwa A, Okada K, Ueshima S, et al. alpha2-antiplasmin is associated with the progression of fibrosis. Am J Pathol. 2010;176:238-45 pubmed publisher
    ..Our findings suggest that alpha2AP is associated with the progression of fibrosis, and regulation of alpha2AP expression by the ERK1/2 and JNK pathways may be an effective antifibrotic therapy for the treatment of systemic sclerosis. ..
  4. Okada K, Lijnen H, Dewerchin M, Belayew A, Matsuo O, Collen D, et al. Characterization and targeting of the murine alpha2-antiplasmin gene. Thromb Haemost. 1997;78:1104-10 pubmed
    ..These targeted clones will be used to generate alpha2-AP deficient mice. ..
  5. Kawashita E, Kanno Y, Asayama H, Okada K, Ueshima S, Matsuo O, et al. Involvement of ?2-antiplasmin in dendritic growth of hippocampal neurons. J Neurochem. 2013;126:58-69 pubmed publisher
    ..Therefore, our findings suggest that ?2AP induces dendritic growth in hippocampal neurons through p38 MAPK activation, independent of plasmin, providing new insights into the role of ?2AP in the CNS. ..
  6. Menoud P, Sappino N, Boudal Khoshbeen M, Vassalli J, Sappino A. The kidney is a major site of alpha(2)-antiplasmin production. J Clin Invest. 1996;97:2478-84 pubmed
    ..Our observations indicate that alpha2-AP can be synthesized in a number of tissues, where it could function as a distal regulator of plasmin-mediated extracellular proteolysis. ..
  7. Law R, Sofian T, Kan W, Horvath A, Hitchen C, Langendorf C, et al. X-ray crystal structure of the fibrinolysis inhibitor alpha2-antiplasmin. Blood. 2008;111:2049-52 pubmed
    The serpin alpha(2)-antiplasmin (SERPINF2) is the principal inhibitor of plasmin and inhibits fibrinolysis. Accordingly, alpha(2)-antiplasmin deficiency in humans results in uncontrolled fibrinolysis and a bleeding disorder...
  8. Kanno Y, Shu E, Kanoh H, Seishima M. The Antifibrotic Effect of α2AP Neutralization in Systemic Sclerosis Dermal Fibroblasts and Mouse Models of Systemic Sclerosis. J Invest Dermatol. 2016;136:762-769 pubmed publisher
    ..Our findings demonstrated that α2AP has a profibrotic effect probably not by the action as a plasmin inhibitor, and that the blocking of α2AP exerts an antifibrotic effect in humans and mice with SSc. ..
  9. Kawashita E, Kanno Y, Ikeda K, Kuretake H, Matsuo O, Matsuno H. Altered behavior in mice with deletion of the alpha2-antiplasmin gene. PLoS ONE. 2014;9:e97947 pubmed publisher
    ..Therefore, our findings suggest that ?2AP is a crucial mediator of motor function, cognitive function, anxiety-like behavior and depression-like behavior, providing new insights into the role of ?2AP in the brain functions. ..

More Information


  1. Lijnen H, Okada K, Matsuo O, Collen D, Dewerchin M. Alpha2-antiplasmin gene deficiency in mice is associated with enhanced fibrinolytic potential without overt bleeding. Blood. 1999;93:2274-81 pubmed
    ..005). Thus, alpha2-AP-/- mice develop and reproduce normally; they have an enhanced endogenous fibrinolytic capacity without overt bleeding. ..
  2. Hayashido Y, Hamana T, Ishida Y, Shintani T, Koizumi K, Okamoto T. Induction of alpha2-antiplasmin inhibits E-cadherin processing mediated by the plasminogen activator/plasmin system, leading to suppression of progression of oral squamous cell carcinoma via upregulation of cell-cell adhesion. Oncol Rep. 2007;17:417-23 pubmed
    ..These results suggested that downregulation of the plasminogen activator/ plasmin system by alpha2-AP might be a potent therapeutic approach to prevent the progression of oral SCC. ..
  3. Eddy J, Schroeder J, Zimbler D, Bellows L, Lathem W. Impact of the Pla protease substrate α2-antiplasmin on the progression of primary pneumonic plague. Infect Immun. 2015;83:4837-47 pubmed publisher
  4. Tjwa M, Janssens S, Carmeliet P. Plasmin therapy enhances mobilization of HPCs after G-CSF. Blood. 2008;112:4048-50 pubmed publisher
    ..Moreover, thrombolytic agents, such as tenecteplase and microplasmin, enhance HPC mobilization in mice and humans. Taken together, these findings identify a novel role for plasmin in augmenting HPC mobilization in response to G-CSF. ..
  5. Byrnes J, Duval C, Wang Y, Hansen C, Ahn B, Mooberry M, et al. Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking. Blood. 2015;126:1940-8 pubmed publisher
    ..These findings expose a newly recognized, essential role for fibrin crosslinking during whole blood clot formation and consolidation and establish FXIIIa activity as a key determinant of thrombus composition and size. ..
  6. Lijnen H, Van Hoef B, Dewerchin M, Collen D. Alpha(2)-antiplasmin gene deficiency in mice does not affect neointima formation after vascular injury. Arterioscler Thromb Vasc Biol. 2000;20:1488-92 pubmed
  7. Kawasaki T, Dewerchin M, Lijnen H, Vermylen J, Hoylaerts M. Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice. Blood. 2000;96:153-60 pubmed
    ..Hence, during acute thrombosis, fibrinolysis is efficiently prevented by plasma alpha(2)-AP, but also by vascular PAI-1, locally released into the circulation after endothelial injury. ..
  8. Kanno Y, Ishisaki A, Kuretake H, Maruyama C, Matsuda A, Matsuo O. α2-antiplasmin modulates bone formation by negatively regulating osteoblast differentiation and function. Int J Mol Med. 2017;40:854-858 pubmed publisher
    ..These results suggest that α2AP negatively affects OB differentiation and function by inhibiting the Wnt/β-catenin pathway. These findings provide a basis for clinical strategies to improve various bone disorders. ..
  9. Nagai N, De Mol M, Lijnen H, Carmeliet P, Collen D. Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice. Circulation. 1999;99:2440-4 pubmed
    ..Inhibition of alpha2-AP may constitute a potential avenue to treatment of FCI. ..
  10. Kitching A, Turner A, O Sullivan K, Dewerchin M, Lijnen H. Endogenous alpha2-antiplasmin does not enhance glomerular fibrin deposition or injury in glomerulonephritis. J Thromb Haemost. 2003;1:1992-9 pubmed
    ..19 +/- 0.01, alpha2-AP-/- 0.36 +/- 0.03 lyzed area/total area). alpha2-AP is not important to net glomerular fibrin deposition, crescent formation or renal impairment in crescentic GN. ..
  11. L hteenm ki K, Kyll nen P, Partanen L, Korhonen T. Antiprotease inactivation by Salmonella enterica released from infected macrophages. Cell Microbiol. 2005;7:529-38 pubmed publisher
    ..The results suggest that intracellular enhancement of PgtE activity in Salmonella may promote macrophage-associated proteolysis and cellular migration by altering the balance between host plasmin and alpha(2)AP...
  12. Matsuno H, Ishisaki A, Nakajima K, Okada K, Ueshima S, Matsuo O, et al. Lack of alpha 2-antiplasmin promotes re-endothelialization via over-release of VEGF after vascular injury in mice. Blood. 2003;102:3621-8 pubmed
    ..Our results provide new insight into the role of alpha 2-AP and VEGF in the pathogenesis of re-endothelialization following vascular injury. ..
  13. Mandel S, Rechavi G, Gozes I. Activity-dependent neuroprotective protein (ADNP) differentially interacts with chromatin to regulate genes essential for embryogenesis. Dev Biol. 2007;303:814-24 pubmed
    ..These results place ADNP at a crucial point of gene regulation, repressing potential endoderm genes and enhancing genes associated with organogenesis/neurogenesis. ..
  14. Kanno Y, Hirade K, Ishisaki A, Nakajima K, Suga H, Into T, et al. Lack of alpha2-antiplasmin improves cutaneous wound healing via over-released vascular endothelial growth factor-induced angiogenesis in wound lesions. J Thromb Haemost. 2006;4:1602-10 pubmed
    ..This is the first report to describe the crucial role that alpha(2)AP plays following angiogenesis in the process of wound healing. Our results provide new insight into the role of alpha(2)AP on cutaneous wound healing. ..
  15. Matsuno H, Okada K, Ueshima S, Matsuo O, Kozawa O. Alpha2-antiplasmin plays a significant role in acute pulmonary embolism. J Thromb Haemost. 2003;1:1734-9 pubmed
    ..Therefore, the combination of inhibition of alpha2-AP with thrombolytic therapy could be beneficial in the treatment of acute PE. ..
  16. Lijnen H, Van Hoef B, Beelen V, Collen D. Characterization of the murine plasma fibrinolytic system. Eur J Biochem. 1994;224:863-71 pubmed
  17. Reed G, Houng A, Wang D. Microvascular thrombosis, fibrinolysis, ischemic injury, and death after cerebral thromboembolism are affected by levels of circulating α2-antiplasmin. Arterioscler Thromb Vasc Biol. 2014;34:2586-93 pubmed publisher
    ..By comparison to TPA, the protective effects of a2AP deficiency or inactivation seem to be mediated through reductions in microvascular thrombosis and matrix metalloproteinase-9 expression. ..
  18. Kawasaki T, Dewerchin M, Lijnen H, Vreys I, Vermylen J, Hoylaerts M. Mouse carotid artery ligation induces platelet-leukocyte-dependent luminal fibrin, required for neointima development. Circ Res. 2001;88:159-66 pubmed
    ..Delayed coagulation then results in formation of a fibrin matrix, which is used by smooth muscle cells to migrate into the lumen. ..
  19. Okada K, Ueshima S, Imano M, Kataoka K, Matsuo O. The regulation of liver regeneration by the plasmin/alpha 2-antiplasmin system. J Hepatol. 2004;40:110-6 pubmed
    ..These results suggest that the plasmin/alpha(2)-AP system played an important role in hepatic repair via clearance from the injury area. ..
  20. Okada K, Ueshima S, Kawao N, Yano M, Tamura Y, Tanaka M, et al. Lack of both ?2-antiplasmin and plasminogen activator inhibitor type-1 induces high IgE production. Life Sci. 2013;93:89-95 pubmed publisher
    ..Moreover, it is suggested that both ?2-AP and PAI-1 are involved in the recruitment of lymphocytes in the peripheral tissues. ..