Regulation of Vascular Endothelial Growth Factor Expression in Cultured Keratinocytes.
Open accessAbstract
Recent in situ hybridization studies had demonstrated a strong increase in vascular endothelial growth factor (VEGF) mRNA expression in the hyperproliferative epithelium during wound healing. To determine potential mediators of VEGF induction during this process, we analyzed the regulation of VEGF expression in cultured human keratinocytes. We found a large induction of VEGF expression upon treatment of quiescent cells with serum, epidermal growth factor, transforming growth factor-beta 1, keratinocyte growth factor, or the proinflammatory cytokine tumor necrosis factor alpha, respectively. Since all these factors are present at the wound site during the early phase of wound healing, they might also be responsible for VEGF induction after cutaneous injury. To determine the importance of increased VEGF production for wound repair, we compared the time course of VEGF mRNA expression during wound healing of healthy control mice with the kinetics of VEGF expression during skin repair of genetically diabetic db/db mice which are characterized by impaired wound healing. In normal mice we found elevated VEGF mRNA levels during the period when granulation tissue formation occurs. In contrast, VEGF mRNA levels even declined during this period in db/db mice, suggesting that a defect in VEGF regulation might be associated with wound healing disorders.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
VEGF is a cytokine released by macrophages and keratinocytes during wound reconstruction to promote angiogenesis.
“Vascular endothelial growth factor, or VEGF, is a cytokine released by macrophages and keratinocytes during wound reconstruction to promote angiogenesis.195–197”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [197]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Lindemann, A., Riedel, D., Oster, W., et al. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114016 · Cited by 190 · see citing works
RetractedVascular Endothelial Growth Factor Is a Secreted Angiogenic Mitogen
Leung, D. W., Cachianes, G., Kuang, W.-J., Goeddel, D. V., & Ferrara, N. (1989) · Science · doi:10.1126/science.2479986 · Cited by 4,988 · see citing works
Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line.
Boukamp, P., Petrussevska, R. T., Breitkreutz, D., Hornung, J., Markham, A., & Fusenig, N. E. (1988) · The Journal of cell biology · doi:10.1083/jcb.106.3.761 · Cited by 4,170 · see citing works
Folkman, J., & Klagsbrun, M. (1987) · Science · doi:10.1126/science.2432664 · Cited by 3,783 · see citing works
Roberts, A. B., Sporn, M. B., Assoian, R. K., Smith, J. M., Roche, N. S., Wakefield, L. M., Heine, U., Liotta, L. A., Falanga, V., & Kehrl, J. H. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.12.4167 · Cited by 2,867 · see citing works
Vascular Permeability Factor, an Endothelial Cell Mitogen Related to PDGF
Keck, P. J., Hauser, S. D., Krivi, G. G., Sanzo, K., Warren, T. G., Feder, J., & Connolly, D. T. (1989) · Science · doi:10.1126/science.2479987 · Cited by 2,058 · see citing works
The fms -Like Tyrosine Kinase, a Receptor for Vascular Endothelial Growth Factor
de Vries, C. J. M., Escobedo, J. A., Ueno, H., Houck, K. A., Ferrara, N., & Williams, L. T. (1992) · Science · doi:10.1126/science.1312256 · Cited by 2,019 · see citing works
Houck, K. A., Ferrara, N., Winer, J., Cachianes, G., Li, B., & Leung, D. W. (1991) · Molecular Endocrinology · doi:10.1210/mend-5-12-1806 · Cited by 1,364 · see citing works
Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis.
Connolly, D. T., Heuvelman, D. M., Nelson, R. M., Olander, J. V., Eppley, B. L., Delfino, J. J., Siegel, N. R., Leimgruber, R. M., & Feder, J. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114322 · Cited by 1,265 · see citing works
Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α
Leibovich, S. J., Polverini, P. J., Shepard, H. M., Wiseman, D. M., Shively, V. P., & Nuseir, N. (1987) · Nature · doi:10.1038/329630a0 · Cited by 1,207 · see citing works
Wound Macrophages Express TGF-α and Other Growth Factors in Vivo: Analysis by mRNA Phenotyping
Rappolee, D. A., Mark, D., Banda, M. J., & Werb, Z. (1988) · Science · doi:10.1126/science.3041594 · Cited by 1,101 · see citing works
Breier, G., Albrecht, U., Sterrer, S., & Risau, W. (1992) · Development · doi:10.1242/dev.114.2.521 · Cited by 1,087 · see citing works
Self-citationKlagsbrun, M., & D'Amore, P. A. (1991) · Annual Review of Physiology · doi:10.1146/annurev.ph.53.030191.001245 · Cited by 961 · see citing works
Brown, L. F., Yeo, K. T., Berse, B., Yeo, T. K., Senger, D. R., Dvorak, H. F., & van de Water, L. (1992) · The Journal of experimental medicine · doi:10.1084/jem.176.5.1375 · Cited by 878 · see citing works
Grossman, R., Krueger, J. G., Yourish, D., Granelli‐Piperno, A., Murphy, D. P., May, L. T., Kupper, T. S., Sehgal, P. B., & Gottlieb, A. B. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.16.6367 · Cited by 854 · see citing works
Transforming Growth Factor-α: a More Potent Angiogenic Mediator than Epidermal Growth Factor
Schreiber, A. B., Winkler, M. E., & Derynck, R. (1986) · Science · doi:10.1126/science.2422759 · Cited by 844 · see citing works
Purification and characterization of a newly identified growth factor specific for epithelial cells.
Rubin, J. S., Osada, H., Finch, P. W., Taylor, W., Rudikoff, S., & Aaronson, S. A. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.3.802 · Cited by 832 · see citing works
Physiology, Biochemistry, and Molecular Biology of the Skin
Shelley, W. B. (1992) · JAMA · doi:10.1001/jama.1992.03490040129042 · Cited by 791 · see citing works
Barrandon, Y., & Green, H. (1987) · Cell · doi:10.1016/0092-8674(87)90179-6 · Cited by 702 · see citing works
Fràter‐Schröder, M., Risau, W., Hallmann, R., Gautschi-Sova, P., & Böhlen, P. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.15.5277 · Cited by 698 · see citing works
PDGF and FGF stimulate wound healing in the genetically diabetic mouse.
Greenhalgh, D. G., Sprugel, K. H., Murray, M. J., & Ross, R. (1990) · Europe PMC (PubMed Central) · Cited by 681 · see citing works
Self-citationLarge induction of keratinocyte growth factor expression in the dermis during wound healing
Werner, S., Peters, K. G., Longaker, M. T., Fuller-Pace, F., Banda, M. J., & Williams, L. T. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.15.6896 · Cited by 612 · see citing works
Self-citationThe Function of KGF in Morphogenesis of Epithelium and Reepithelialization of Wounds
Werner, S., Smola, H., Liao, X., Longaker, M. T., Krieg, T. M., HOFSCHNEIDER, P. H., & Williams, L. T. (1994) · Science · doi:10.1126/science.7973639 · Cited by 604 · see citing works
Self-citationGospodarowicz, D., Abraham, J. A., & Schilling, J. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7311 · Cited by 563 · see citing works
Shipley, G. D., Pittelkow, M. R., Wille, J. J., Scott, R. E., & Moses, H. L. (1986) · PubMed · Cited by 553 · see citing works
Goldman, C. K., Kim, J., Wong, W., King, V. J., Brock, T. A., & Gillespie, G. Y. (1993) · Molecular Biology of the Cell · doi:10.1091/mbc.4.1.121 · Cited by 531 · see citing works
Peters, K. G., de Vries, C., & Williams, L. T. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.8915 · Cited by 462 · see citing works
Martinet, Y., Bitterman, P. B., Mornex, J., Grotendorst, G. R., Martin, G. R., & Crystal, R. G. (1986) · Nature · doi:10.1038/319158a0 · Cited by 370 · see citing works
Diabetes-Obesity Syndromes in Mice
Coleman, D. L. (1982) · Diabetes · doi:10.2337/diab.31.1.s1 · Cited by 354 · see citing works
Induction of transforming growth factor-α in activated human alveolar macrophages
Madtes, D. K., Raines, E. W., Sakaríassen, K. S., Assoian, R. K., Sporn, M. B., Bell, G. I., & Ross, R. (1988) · Cell · doi:10.1016/0092-8674(88)90390-x · Cited by 345 · see citing works
Kopan, R., Traska, G., & Fuchs, E. V. (1987) · The Journal of Cell Biology · doi:10.1083/jcb.105.1.427 · Cited by 339 · see citing works
Coffey, R. J., Bascom, C. C., Sipes, N. J., Graves‐Deal, R., Weissman, B. E., & Moses, H. L. (1988) · Molecular and Cellular Biology · doi:10.1128/mcb.8.8.3088 · Cited by 320 · see citing works
Baird, A., & Durkin, T. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(86)90305-0 · Cited by 308 · see citing works
Transforming growth factor-beta inhibits endothelial cell proliferation
Fràter‐Schröder, M., Müller, G. I., Birchmeier, W., & Böhlen, P. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(86)91209-x · Cited by 307 · see citing works
Platelet-Derived Growth Factor is Angiogenic In Vivo
Risau, W., Drexler, H. C. A., Mironov, V., Smits, A., Siegbahn, A., Funa, K., & Heldin, C. (1992) · Growth Factors · doi:10.3109/08977199209046408 · Cited by 283 · see citing works
Werner, S., Breeden, M. P., Hübner, G., Greenhalgh, D. G., & Longaker, M. T. (1994) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12395564 · Cited by 282 · see citing works
Self-citationMonocyte-Derived Human B-Cell Growth Factor Identified as Interferon-β 2 (BSF-2, IL-6)
Tosato, G., Seamon, K. B., Goldman, N. D., Sehgal, P. B., May, L. T., Washington, G. C., Jones, K. D., & Pike, S. E. (1988) · Science · doi:10.1126/science.2829354 · Cited by 272 · see citing works
Chapter 15 Serial Cultivation of Normal Human Epidermal Keratinocytes
Rheinwald, J. G. (1980) · Methods in cell biology · doi:10.1016/s0091-679x(08)60769-4 · Cited by 266 · see citing works
Regulation of keratinocyte growth factor gene expression by interleukin 1.
Chedid, M., Rubin, J. S., Csaky, K. G., & Aaronson, S. A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34123-6 · Cited by 218 · see citing works
Brauchle, M. A., Angermeyer, K., Hübner, G., & Werner, S. (1994) · PubMed · Cited by 203 · see citing works
Self-citationCicco, N., Lindemann, A., Content, J., Vandenbussche, P., Lübbert, M., Gauss, J., Mertelsmann, R. H., & Herrmann, F. R. (1990) · Blood · doi:10.1182/blood.v75.10.2049.2049 · Cited by 193 · see citing works
Risau, W. (1990) · Progress in Growth Factor Research · doi:10.1016/0955-2235(90)90010-h · Cited by 191 · see citing works
AIDS-associated kaposi's sarcoma cells in culture express vascular endothelial growth factor
Weindel, K., Marmé, D., & Weich, H. A. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)80313-4 · Cited by 163 · see citing works
Expression of interleukin-1 alpha and beta genes by human blood polymorphonuclear leukocytes.
Lord, P. C. W., Wilmoth, L. M., Mizel, S. B., et al. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115134 · Cited by 156 · see citing works
Davison, J. M., Sheills, E. A., Barron, W. M., ROBINSON, A. G., & Lindheimer, M. D. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114017 · Cited by 134 · see citing works
Fibrinogen influx and accumulation of cross-linked fibrin in healing wounds and in tumor stroma.
Brown, L. F., Water, L. V. D., Harvey, V. S., & Dvorak, H. F. (1988) · PubMed Central · Cited by 107 · see citing works
Sauder, D. N., Stanulis‐Praeger, B. M., & Gilchrest, B. A. (1988) · Archives of Dermatological Research · doi:10.1007/bf00417707 · Cited by 106 · see citing works
Symington, F. W. (1989) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12696816 · Cited by 96 · see citing works
Flagged first, then by citations
Research works printed but not linked: 10
- Clark, R. A. F. (1991) in Physiology, Biochemistry, and Molecular Biology ofthe Skin (Goldsmith, L. A., ed) pp. 576-601, Oxford University Press, Oxford
- Roberts, A. B., Sporn, M. B., Assoian, R. K, Smith, J. M., Roche, N. S., Wakefield, L. M., Heine, U. L, Liotta, L. A., Falanga, V. Kehrl, J. H., and Fauci, A. S. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 4167-4171
- Frater-Schroder, M., Risau, W., Hallmann, R., Gautschi, P., and Bohlen, P. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 5277-5281
- Gospodarowicz, D., Abraham, J. A., and Schilling, J. (1989) Proc. Natl. Acad. Sci. U. S. A. 86,7311-7315
- Peters, K. G., deVries, C., and Williams, L. T. (1993) Proc. Nat!. Acad. Sci.
- Werner, S., Peters, K. G., Longaker, M. T., Fuller-Pace, F., Banda, M., and Williams, L. T. (1992) Proc. Natl. Acad. Sci. U. S. A. 89,6896-6900
- Rubin, J. S., Osada, H., Finch, P. W., Taylor, W. G., Rudikoff, S., and Aaronson, S. A. (1989) Proc. Nat!. Acad. Sci. U. S. A. 86,802-806
- Grossman, R. M., Krueger, J., Yourish, D., Granelli-Piperno, A., Murphy, D. P., May, L. T., Kupper, T. S., Sehgal, P. B., and Gottlieb, A. B. (1989) Proc. Nat!. Acad. Sci. U. S. A. 86, 6367-6371
- Dinarello, C. A. (1991) in The Cytokine Handbook (Thomson, A. W., ed) pp. 47-82, Academic Press, New York
- Wong, H. L., and Wahl, S. M. (1989) in Human Monocytes (Zembala, M., and Asherson, G. L., ed) pp. 383-394, Academic Press, New York
Cited by
Sorted by citations
The molecular biology of chronic wounds and delayed healing in diabetes
Blakytny, R., & Jude, E. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01773.x · Cited by 632 · see citing works
Stabilization of HIF-1α is critical to improve wound healing in diabetic mice
Botusan, I. R., Sunkari, V. G., Savu, O., Catrina, A. I., Grünler, J., Lindberg, S., Pereira, T., Ylä-Herttuala, S., Poellinger, L., Brismar, K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805230105 · Cited by 533 · see citing works
Obesity, adipocytokines, and insulin resistance in breast cancer
Rose, D. P., Komninou, D., & Stephenson, G. D. (2004) · Obesity Reviews · doi:10.1111/j.1467-789x.2004.00142.x · Cited by 460 · see citing works
Braun, S., Hanselmann, C., Gassmann, M. G., auf dem Keller, U., Born-Berclaz, C., Chan, K., Kan, Y. W., & Werner, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5492-5505.2002 · Cited by 410 · see citing works
Self-citationRegulation of angiogenesis: Wound healing as a model
EMING, S., BRACHVOGEL, B., ODORISIO, T., & KOCH, M. (2007) · Progress in Histochemistry and Cytochemistry · doi:10.1016/j.proghi.2007.06.001 · Cited by 392 · see citing works
Impaired wound healing and angiogenesis in eNOS-deficient mice
Lee, P. C., Salyapongse, A. N., Bragdon, G. A., Shears, L. L., Watkins, S. C., Edington, H. D. J., & Billiar, T. R. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.4.h1600 · Cited by 369 · see citing works
Expression and Proteolysis of Vascular Endothelial Growth Factor is Increased in Chronic Wounds
Lauer, G., Sollberg, S., Cole, M., Krieg, T., Eming, S. A., Flamme, I., Stürzebecher, J., & Mann, K. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00036.x · Cited by 349 · see citing works
Biocompatible Materials for Continuous Glucose Monitoring Devices
Nichols, S. P., Koh, A., Storm, W. L., Shin, J. H., & Schoenfisch, M. H. (2013) · Chemical Reviews · doi:10.1021/cr300387j · Cited by 347 · see citing works
Milanini, J., Viñals, F., Pouysségur, J., & Pagès, G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18165 · Cited by 315 · see citing works
Reduced expression of PDGF and PDGF receptors during impaired wound healing
Beer, H.-D., Longaker, M. T., & Werner, S. (1997) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12319188 · Cited by 257 · see citing works
Self-citationPagès, G., Berra, E., Milanini, J., Levy, A. P., & Pouysségur, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002104200 · Cited by 184 · see citing works
Facilitating action of asiaticoside at low doses on burn wound repair and its mechanism
Kimura, Y., Sumiyoshi, M., Samukawa, K.-I., Satake, N., & Sakanaka, M. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.02.036 · Cited by 126 · see citing works
Supp, D. M., Supp, A. P., Boyce, S. T., & Bell, S. M. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00824.x · Cited by 120 · see citing works
Glucocorticoid-regulated gene expression during cutaneous wound repair
BEER, H.-D., Fässler, R., & Werner, S. (2000) · Vitamins & Hormones · doi:10.1016/s0083-6729(00)59008-6 · Cited by 113 · see citing works
Self-citationObara, K., Ishihara, M., Fujita, M., Kanatani, Y., Hattori, H., Matsui, T., Takase, B., Ozeki, Y., Nakamura, S., Ishizuka, T., et al. (2005) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2005.130406.x · Cited by 97 · see citing works
Schobersberger, W., Hobisch-Hagen, P., Fries, D., Wiedermann, F., Rieder-Scharinger, J., Villiger, B., Frey, W., Herold, M., Fuchs, D., & Jelkmann, W. (2000) · Immunobiology · doi:10.1016/s0171-2985(00)80078-9 · Cited by 83 · see citing works
HoxD3 Accelerates Wound Healing in Diabetic Mice
Hansen, S. L., Myers, C. A., Charboneau, A., Young, D. M., & Boudreau, N. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63597-3 · Cited by 82 · see citing works
The promotion of endothelial cell attachment and spreading using FNIII10 fused to VEGF-A165
Traub, S., Morgner, J., Martino, M. M., Höning, S., Swartz, M. A., Wickström, S. A., Hubbell, J. A., & Eming, S. A. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.04.050 · Cited by 42 · see citing works
Qin, D., Lee, W.-H., Gao, Z., Zhang, W., Peng, M., Sun, T., & Gao, Y. (2018) · Peptides · doi:10.1016/j.peptides.2018.01.009 · Cited by 27 · see citing works
Chen, T.-S., Lai, Y.-A., Lai, Y.-J., & Chien, C.-T. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120969 · Cited by 12 · see citing works
- Authors
- Frank, S., Hübner, G., Breier, G., Longaker, M. T., Greenhalgh, D. G., & Werner, S.
- Affiliations
- Max Planck Institute of Biochemistry (DE)
- Max Planck Society (DE)
- NYU Langone Health (US)
- University of Cincinnati (US)
- Corresponding author
- Werner, Sabine
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1995-05
- Volume
- 270
- Issue
- 21
- Pages
- 12607-12613
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1550364580
- Cited by
- 764
- References
- 48
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 18 · 2023: 21 · 2022: 22 · 2021: 18 · 2020: 14 · 2019: 17 · 2018: 23 · 2017: 16 · 2016: 16 · 2015: 34 · 2014: 23 · 2013: 18 · 2012: 24
- FWCI
- 45.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Keywords
- vascular endothelial growth factor, keratinocytes, wound healing, VEGF mRNA expression, epidermal growth factor, TGF-β1, keratinocyte growth factor, TNF-α, diabetic wound healing, db/db mice, granulation tissue, skin wounds
- MeSH terms
- Animals, Cells, Cultured, Diabetes Mellitus, Dose-Response Relationship, Drug, Epidermal Growth Factor, Fibroblast Growth Factors, Gene Expression Regulation, Growth Substances, Lymphokines, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, RNA, Messenger, Tumor Necrosis Factor-alpha, Wound Healing, Keratinocytes, Endothelial Growth Factors, Interleukin-10, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Mice, Fibroblast Growth Factor 7, Fibroblast Growth Factor 10
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review