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Gene Review

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

Homo sapiens

Synonyms: Cell proliferation-inducing gene 35 protein, EPC-1, OI12, OI6, PEDF, ...
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Disease relevance of SERPINF1


High impact information on SERPINF1


Chemical compound and disease context of SERPINF1


Biological context of SERPINF1


Anatomical context of SERPINF1


Associations of SERPINF1 with chemical compounds

  • Pigment epithelium-derived factor (PEDF) is a multiple functional protein, coded by the serine proteinase inhibitor, clade F, member 1 (SERPINF1) gene, which has both anti-angiogenic activity and neurotrophic activity at the same time [17].
  • The structure revealed the organization of possible receptor and heparin-binding sites, and showed that, unlike any other previously characterized serpin, PEDF has a striking asymmetric charge distribution that might be of functional importance [18].
  • The PEDF gene contains a typical signal-peptide sequence, initiator methionine codon, and polyadenylylation signal and matches the size of other members of the serpin superfamily (e.g., alpha 1-antitrypsin) [13].
  • However, treatment of PEDF with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide abolished it, implicating the PEDF aspartic and/or glutamic acid residues in its interaction with collagen I [19].
  • Simultaneous treatments with PEDF inhibited the AGE-elicited VEGF-mediated permeability by down-regulating mRNA levels of p22(phox) and gp91(phox), membrane components of NADPH oxidase, and subsequently decreasing retinal levels of an oxidative stress marker, 8-hydroxydeoxyguanosine [20].

Regulatory relationships of SERPINF1


Other interactions of SERPINF1

  • VEGFR-1 neutralization decreased PEDF mRNA and protein expression whereas anti-VEGFR-2 antibody had no effect [21].
  • Addition of placenta growth factor (PlGF) restored PEDF expression in the presence of anti-VEGF antibody [21].
  • CONCLUSIONS: TA reduces the expression of VEGF but increases the expression of PEDF in ARPE19 and HUVE cells [16].
  • We provide evidence that induction of apoptosis by PEDF is associated with activation of p38 followed by cleavage of caspases 3, 8, and 9 by treatment with PEDF, and PEDF's actions are caspase dependent [12].
  • However, PEDF immunoreactivity was significantly lower in RPE cells (p=0.0073), RPE basal lamina (p=0.0141), Bruch's membrane (p<0.0001), and choroidal stroma (p=0.0161) of AMD choroids [2].

Analytical, diagnostic and therapeutic context of SERPINF1

  • Concurrently, the protein levels of VEGF and PEDF in ARPE cells were detected with ELISA [16].
  • Tissues were cryopreserved and streptavidin alkaline phosphatase immunohistochemistry was performed with rabbit polyclonal anti-human VEGF and rabbit polyclonal anti-human PEDF antibodies [2].
  • RESULTS: Real-time RT-PCR showed TA affected a 0.5 fold decrease in VEGF(165) level and about a 2.5 fold increase in PEDF level at both TA concentrations [16].
  • Western blot analysis confirmed that the average PEDF level in pterygia was drastically lower than those in normal corneal and conjunctival tissues, respectively [26].
  • Angiogenic activity in samples of patients from the control group was generally inhibitory due to PEDF, and inhibition was blocked by neutralizing antibodies to PEDF [3].


  1. Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site. Liu, H., Ren, J.G., Cooper, W.L., Hawkins, C.E., Cowan, M.R., Tong, P.Y. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration. Bhutto, I.A., McLeod, D.S., Hasegawa, T., Kim, S.Y., Merges, C., Tong, P., Lutty, G.A. Exp. Eye Res. (2006) [Pubmed]
  3. Proliferative diabetic retinopathy is associated with a low level of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor. a pilot study. Boehm, B.O., Lang, G., Feldmann, B., Kurkhaus, A., Rosinger, S., Volpert, O., Lang, G.K., Bouck, N. Horm. Metab. Res. (2003) [Pubmed]
  4. Regulation of the expression of pigment epithelium-derived factor, an anti-angiogenic factor in human oral squamous cell carcinoma cell lines. Miyagishi, D., Ohno-Matsui, K., Amagasa, T., Morita, I. Cancer Lett. (2003) [Pubmed]
  5. Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas. Doll, J.A., Stellmach, V.M., Bouck, N.P., Bergh, A.R., Lee, C., Abramson, L.P., Cornwell, M.L., Pins, M.R., Borensztajn, J., Crawford, S.E. Nat. Med. (2003) [Pubmed]
  6. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Dawson, D.W., Volpert, O.V., Gillis, P., Crawford, S.E., Xu, H., Benedict, W., Bouck, N.P. Science (1999) [Pubmed]
  7. PEDF: bridging neurovascular interactions in the stem cell niche. Pumiglia, K., Temple, S. Nat. Neurosci. (2006) [Pubmed]
  8. Salutary effect of pigment epithelium-derived factor in diabetic nephropathy: evidence for antifibrogenic activities. Wang, J.J., Zhang, S.X., Mott, R., Knapp, R.R., Cao, W., Lau, K., Ma, J.X. Diabetes (2006) [Pubmed]
  9. Decreased expression of pigment epithelium-derived factor is involved in the pathogenesis of diabetic nephropathy. Wang, J.J., Zhang, S.X., Lu, K., Chen, Y., Mott, R., Sato, S., Ma, J.X. Diabetes (2005) [Pubmed]
  10. Azelnidipine, a dihydropyridine-based calcium antagonist, inhibits angiotensin II-induced oxidative stress generation and downregulation of pigment epithelium-derived factor mRNA levels in microvascular endothelial cells. Matsui, T., Yamagishi, S., Nakamura, K., Kikuchi, S., Inoue, H. Drugs under experimental and clinical research. (2005) [Pubmed]
  11. Pigment epithelium-derived factor (PEDF) prevents diabetes- or advanced glycation end products (AGE)-elicited retinal leukostasis. Yamagishi, S., Matsui, T., Nakamura, K., Takeuchi, M., Imaizumi, T. Microvasc. Res. (2006) [Pubmed]
  12. PEDF induces apoptosis in human endothelial cells by activating p38 MAP kinase dependent cleavage of multiple caspases. Chen, L., Zhang, S.S., Barnstable, C.J., Tombran-Tink, J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  13. Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Steele, F.R., Chader, G.J., Johnson, L.V., Tombran-Tink, J. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  14. Extracellular phosphorylation converts pigment epithelium-derived factor from a neurotrophic to an antiangiogenic factor. Maik-Rachline, G., Shaltiel, S., Seger, R. Blood (2005) [Pubmed]
  15. Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma. Matsumoto, K., Ishikawa, H., Nishimura, D., Hamasaki, K., Nakao, K., Eguchi, K. Hepatology (2004) [Pubmed]
  16. Effects of triamcinolone on the expression of VEGF and PEDF in human retinal pigment epithelial and human umbilical vein endothelial cells. Tong, J.P., Lam, D.S., Chan, W.M., Choy, K.W., Chan, K.P., Pang, C.P. Mol. Vis. (2006) [Pubmed]
  17. How PEDF prevents angiogenesis: a hypothesized pathway. Ren, J.G., Jie, C., Talbot, C. Med. Hypotheses (2005) [Pubmed]
  18. Crystal structure of human PEDF, a potent anti-angiogenic and neurite growth-promoting factor. Simonovic, M., Gettins, P.G., Volz, K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  19. Mapping the type I collagen-binding site on pigment epithelium-derived factor. Implications for its antiangiogenic activity. Meyer, C., Notari, L., Becerra, S.P. J. Biol. Chem. (2002) [Pubmed]
  20. Pigment epithelium-derived factor inhibits advanced glycation end product-induced retinal vascular hyperpermeability by blocking reactive oxygen species-mediated vascular endothelial growth factor expression. Yamagishi, S., Nakamura, K., Matsui, T., Inagaki, Y., Takenaka, K., Jinnouchi, Y., Yoshida, Y., Matsuura, T., Narama, I., Motomiya, Y., Takeuchi, M., Inoue, H., Yoshimura, A., Bucala, R., Imaizumi, T. J. Biol. Chem. (2006) [Pubmed]
  21. Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells. Ohno-Matsui, K., Yoshida, T., Uetama, T., Mochizuki, M., Morita, I. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  22. Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative mechanism of PEDF. Yamagishi, S., Nakamura, K., Ueda, S., Kato, S., Imaizumi, T. Cell Tissue Res. (2005) [Pubmed]
  23. Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: a role in aberrant angiogenesis. Cosgrove, G.P., Brown, K.K., Schiemann, W.P., Serls, A.E., Parr, J.E., Geraci, M.W., Schwarz, M.I., Cool, C.D., Worthen, G.S. Am. J. Respir. Crit. Care Med. (2004) [Pubmed]
  24. Pigment-epithelium-derived factor (PEDF) occurs at a physiologically relevant concentration in human blood: purification and characterization. Petersen, S.V., Valnickova, Z., Enghild, J.J. Biochem. J. (2003) [Pubmed]
  25. Pigment epithelium-derived factor (PEDF)-induced apoptosis and inhibition of vascular endothelial growth factor (VEGF) expression in MG63 human osteosarcoma cells. Takenaka, K., Yamagishi, S., Jinnouchi, Y., Nakamura, K., Matsui, T., Imaizumi, T. Life Sci. (2005) [Pubmed]
  26. Decreased pigment epithelium-derived factor and increased vascular endothelial growth factor levels in pterygia. Jin, J., Guan, M., Sima, J., Gao, G., Zhang, M., Liu, Z., Fant, J., Ma, J.X. Cornea (2003) [Pubmed]
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