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Gene Review

SERPINF1  -  serpin peptidase inhibitor, clade F (alpha...

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Disease relevance of SERPINF1

  • Recently, decreased levels of pigment epithelium-derived factor (PEDF) in the eye have been found to predict progression of diabetic retinopathy [1].
  • Expression analysis in stably transfected baby hamster kidney cells shows that the recombinant bovine protein is secreted to the culture media as a mature 50,000-Mr protein, which induces neurite-outgrowth on retinoblastoma cells, like the naturally-occurring PEDF protein [2].
  • This may represent a novel mechanism of ocular angiogenic homeostasis sufficient in the control of PEDF levels during normoxia or mild hypoxia but supplemented by other (hitherto unknown) mechanisms in cases of strong hypoxia [3].
  • The anti-angiogenic activity of pigment epithelium-derived factor (PEDF) has recently been discovered on the basis of its inhibition of ischemia-induced retinal neovascularization in an animal model of retinopathy of the premature [4].
  • Confocal microscopy showed that fluorescein-conjugated PEDF stained exclusively the inner segments of photoreceptors and cells of the ganglion cell layer in retinal cryosections [5].

High impact information on SERPINF1

  • The PEDF protein is secreted in vivo where it constitutes a part of the fetal and adult IPM surrounding photoreceptor outer segments [6].
  • By immunofluorescence, PEDF is localized intracellularly in association with the nucleus, presumptive secretory granules, and cytoskeletal elements of cultured RPE cells with PEDF and actin antibodies colocalizing to the same cytoskeletal structures [6].
  • PEDF mRNA is present in RPE cells of the human eye at 17 weeks of gestation, demonstrating its potential for action in vivo during early retinal development [6].
  • PEDF is thus apparently present intracellularly and extracellularly in both fetal and early adult periods where it could be involved in cellular differentiation and survival and with its loss, in the onset of senescence [6].
  • Analysis of the subcellular distribution of VEGFR-1 revealed the appearance of an 80-kDa C-terminal domain in the cytosol of cells treated with VEGF and PEDF that correlated with a decrease of the full-length receptor in the nuclear and cytoskeletal fractions [7].

Chemical compound and disease context of SERPINF1

  • Here we investigated the ability of PEDF to enhance the survival of hippocampal neurons in culture, and to protect these neurons against acute glutamate toxicity [8].

Biological context of SERPINF1


Anatomical context of SERPINF1

  • Thus, the PEDF induction of neurites must be mediated by a mechanism other than serine protease inhibition [9].
  • However, the effect of PEDF on pericyte growth remains to be unknown [1].
  • Northern analysis of RNA from bovine retinal pigment epithelium (RPE) and neural retina using a human PEDF cDNA fragment reveals expression of the PEDF gene only for RPE [2].
  • Both the growth and the survival of Schwann cells were enhanced by PEDF [10].
  • These findings suggest that in the ischemic retina, Müller cells generate a permissive condition for angiogenesis by secreting more VEGF and less PEDF, but the onset of retinal endothelial cell proliferation requires another triggering signal that remains to be identified [3].

Associations of SERPINF1 with chemical compounds


Regulatory relationships of SERPINF1


Other interactions of SERPINF1

  • The present study suggests that leptin might elicit angiogenesis through VEGF induction as well as PEDF suppression in pericytes and could thus be involved in the development and progression of diabetic retinopathy, especially in obese insulin-resistant patients [14].
  • Furthermore, PEDF increased protein kinase C (PKC) activity in pericytes and staurosporine, a potent cell-permeable inhibitor of PKC, completely blocked the PDGF-B gene induction and subsequent increase in DNA synthesis in PEDF-exposed pericytes [1].
  • An increased ratio of bax to bcl-2 mRNA level with subsequent activation of caspase-3 was observed in high-glucose- or H2O2-exposed pericytes, which was also completely prevented by PEDF [11].

Analytical, diagnostic and therapeutic context of SERPINF1


  1. Pigment epithelium-derived factor (PEDF) promotes growth of pericytes through autocrine production of platelet-derived growth factor-B. Yamagishi, S., Nakamura, K., Takenaka, K., Matsui, T., Jinnouchi, Y., Imaizumi, T. Microvasc. Res. (2005) [Pubmed]
  2. Sequence and expression analysis of bovine pigment epithelium-derived factor. Perez-Mediavilla, L.A., Chew, C., Campochiaro, P.A., Nickells, R.W., Notario, V., Zack, D.J., Becerra, S.P. Biochim. Biophys. Acta (1998) [Pubmed]
  3. PEDF derived from glial Müller cells: a possible regulator of retinal angiogenesis. Eichler, W., Yafai, Y., Keller, T., Wiedemann, P., Reichenbach, A. Exp. Cell Res. (2004) [Pubmed]
  4. Pigment epithelium-derived factor exerts opposite effects on endothelial cells of different phenotypes. Hutchings, H., Maitre-Boube, M., Tombran-Tink, J., Plouët, J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  5. Evidence for pigment epithelium-derived factor receptors in the neural retina. Aymerich, M.S., Alberdi, E.M., Martínez, A., Becerra, S.P. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  6. Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity. Tombran-Tink, J., Shivaram, S.M., Chader, G.J., Johnson, L.V., Bok, D. J. Neurosci. (1995) [Pubmed]
  7. Pigment epithelium-derived factor inhibits angiogenesis via regulated intracellular proteolysis of vascular endothelial growth factor receptor 1. Cai, J., Jiang, W.G., Grant, M.B., Boulton, M. J. Biol. Chem. (2006) [Pubmed]
  8. Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons. DeCoster, M.A., Schabelman, E., Tombran-Tink, J., Bazan, N.G. J. Neurosci. Res. (1999) [Pubmed]
  9. Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop. Becerra, S.P., Sagasti, A., Spinella, P., Notario, V. J. Biol. Chem. (1995) [Pubmed]
  10. Pigment epithelium-derived factor (PEDF) in neuroblastoma: a multifunctional mediator of Schwann cell antitumor activity. Crawford, S.E., Stellmach, V., Ranalli, M., Huang, X., Huang, L., Volpert, O., De Vries, G.H., Abramson, L.P., Bouck, N. J. Cell. Sci. (2001) [Pubmed]
  11. Pigment epithelium-derived factor inhibits oxidative stress-induced apoptosis and dysfunction of cultured retinal pericytes. Amano, S., Yamagishi, S., Inagaki, Y., Nakamura, K., Takeuchi, M., Inoue, H., Imaizumi, T. Microvasc. Res. (2005) [Pubmed]
  12. Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Duh, E.J., Yang, H.S., Suzuma, I., Miyagi, M., Youngman, E., Mori, K., Katai, M., Yan, L., Suzuma, K., West, K., Davarya, S., Tong, P., Gehlbach, P., Pearlman, J., Crabb, J.W., Aiello, L.P., Campochiaro, P.A., Zack, D.J. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  13. Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration. Bilak, M.M., Corse, A.M., Bilak, S.R., Lehar, M., Tombran-Tink, J., Kuncl, R.W. J. Neuropathol. Exp. Neurol. (1999) [Pubmed]
  14. Up-regulation of vascular endothelial growth factor and down-regulation of pigment epithelium-derived factor messenger ribonucleic acid levels in leptin-exposed cultured retinal pericytes. Yamagishi, S., Inagaki, Y., Amano, S., Okamoto, T., Takeuchi, M. International journal of tissue reactions. (2002) [Pubmed]
  15. Suppression of corneal neovascularization by PEDF release from human amniotic membranes. Shao, C., Sima, J., Zhang, S.X., Jin, J., Reinach, P., Wang, Z., Ma, J.X. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
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