Abstract
The stimulatory effect of recombinant basic fibroblast growth factor (bFGF) on wound healing was assessed using healing-impaired (db/db) mice. Full-thickness wounds were made in female diabetic C57BL/KsJ db/db mice, and their normal (db/+) littermates with a punch biopsy instrument. Recombinant bFGF was applied locally to the open wound once a day. The mice were later killed and histological sections of the wounds were prepared. The degree of wound healing was evaluated using several histological parameters such as degree of reepithelialization, granulation tissue thickness, matrix density, number of infiltrated cells, and number of capillaries. Wounds from normal mice displayed good reepithelialization rates and granulation tissue formation, while wounds from db/db mice had poor responses, especially in the dermal parameters. Although the application of bFGF to wounds in the normal (db/+) mice had little effect, application of bFGF to wounds in db/db mice induced significant responses in all of the dermal parameters compared with nontreated db/db mice (p less than 0.001). In the presence of bFGF, these parameters approximated those observed in nontreated littermates. A minimum of 0.5 microgram bFGF in either single or multiple applications was required for a significant effect. bFGF that was either boiled or pretreated with neutralizing antibody had little stimulatory effect. Time-course experiments indicated that the granulation response in bFGF-treated mice peaked between 8 and 12 d, and decreased after 12 d, while matrix density continued to increase until the 18th day (p less than 0.05). The breaking strength of healed linear wounds in db/db mice was also decreased when compared with heterozygous littermates. This parameter was also improved by the administration of bFGF to the wounds (p less than 0.05).
Full Text
The Full Text of this article is available as a PDF (1.0 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brown G. L., Curtsinger L. J., White M., Mitchell R. O., Pietsch J., Nordquist R., von Fraunhofer A., Schultz G. S. Acceleration of tensile strength of incisions treated with EGF and TGF-beta. Ann Surg. 1988 Dec;208(6):788–794. doi: 10.1097/00000658-198812000-00019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown G. L., Curtsinger L., 3rd, Brightwell J. R., Ackerman D. M., Tobin G. R., Polk H. C., Jr, George-Nascimento C., Valenzuela P., Schultz G. S. Enhancement of epidermal regeneration by biosynthetic epidermal growth factor. J Exp Med. 1986 May 1;163(5):1319–1324. doi: 10.1084/jem.163.5.1319. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buckley A., Davidson J. M., Kamerath C. D., Wolt T. B., Woodward S. C. Sustained release of epidermal growth factor accelerates wound repair. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7340–7344. doi: 10.1073/pnas.82.21.7340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buntrock P., Buntrock M., Marx I., Kranz D., Jentzsch K. D., Heder G. Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. III. Electron microscopy, autoradiography, and ultrastructural autoradiography of granulation tissue. Exp Pathol. 1984;26(4):247–254. doi: 10.1016/s0232-1513(84)80057-2. [DOI] [PubMed] [Google Scholar]
- Buntrock P., Jentzsch K. D., Heder G. Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. I. Quantitative and biochemical studies into formation of granulation tissue. Exp Pathol. 1982;21(1):46–53. doi: 10.1016/s0232-1513(82)80051-0. [DOI] [PubMed] [Google Scholar]
- Buntrock P., Jentzsch K. D., Heder G. Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. II. Histological and morphometric examination of cells and capillaries. Exp Pathol. 1982;21(1):62–67. doi: 10.1016/s0232-1513(82)80054-6. [DOI] [PubMed] [Google Scholar]
- Clark R. A. Cutaneous tissue repair: basic biologic considerations. I. J Am Acad Dermatol. 1985 Nov;13(5 Pt 1):701–725. doi: 10.1016/s0190-9622(85)70213-7. [DOI] [PubMed] [Google Scholar]
- Danon D., Kowatch M. A., Roth G. S. Promotion of wound repair in old mice by local injection of macrophages. Proc Natl Acad Sci U S A. 1989 Mar;86(6):2018–2020. doi: 10.1073/pnas.86.6.2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davidson J. M., Klagsbrun M., Hill K. E., Buckley A., Sullivan R., Brewer P. S., Woodward S. C. Accelerated wound repair, cell proliferation, and collagen accumulation are produced by a cartilage-derived growth factor. J Cell Biol. 1985 Apr;100(4):1219–1227. doi: 10.1083/jcb.100.4.1219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folkman J., Klagsbrun M. Angiogenic factors. Science. 1987 Jan 23;235(4787):442–447. doi: 10.1126/science.2432664. [DOI] [PubMed] [Google Scholar]
- Gospodarowicz D., Ferrara N., Schweigerer L., Neufeld G. Structural characterization and biological functions of fibroblast growth factor. Endocr Rev. 1987 May;8(2):95–114. doi: 10.1210/edrv-8-2-95. [DOI] [PubMed] [Google Scholar]
- Grotendorst G. R., Martin G. R., Pencev D., Sodek J., Harvey A. K. Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats. J Clin Invest. 1985 Dec;76(6):2323–2329. doi: 10.1172/JCI112243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Joseph-Silverstein J., Moscatelli D., Rifkin D. B. The development of a quantitative RIA for basic fibroblast growth factor using polyclonal antibodies against the 157 amino acid form of human bFGF. The identification of bFGF in adherent elicited murine peritoneal macrophages. J Immunol Methods. 1988 Jun 13;110(2):183–192. doi: 10.1016/0022-1759(88)90102-0. [DOI] [PubMed] [Google Scholar]
- Lynch S. E., Nixon J. C., Colvin R. B., Antoniades H. N. Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7696–7700. doi: 10.1073/pnas.84.21.7696. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mandel M. A., Mahmoud A. A. Impairment of cell-mediated immunity in mutation diabetic mice (db/db). J Immunol. 1978 Apr;120(4):1375–1377. [PubMed] [Google Scholar]
- McGee G. S., Davidson J. M., Buckley A., Sommer A., Woodward S. C., Aquino A. M., Barbour R., Demetriou A. A. Recombinant basic fibroblast growth factor accelerates wound healing. J Surg Res. 1988 Jul;45(1):145–153. doi: 10.1016/0022-4804(88)90034-0. [DOI] [PubMed] [Google Scholar]
- Mustoe T. A., Pierce G. F., Thomason A., Gramates P., Sporn M. B., Deuel T. F. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science. 1987 Sep 11;237(4820):1333–1336. doi: 10.1126/science.2442813. [DOI] [PubMed] [Google Scholar]
- O'Keefe E. J., Chiu M. L., Payne R. E., Jr Stimulation of growth of keratinocytes by basic fibroblast growth factor. J Invest Dermatol. 1988 May;90(5):767–769. doi: 10.1111/1523-1747.ep12560956. [DOI] [PubMed] [Google Scholar]
- Pierce G. F., Mustoe T. A., Lingelbach J., Masakowski V. R., Gramates P., Deuel T. F. Transforming growth factor beta reverses the glucocorticoid-induced wound-healing deficit in rats: possible regulation in macrophages by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2229–2233. doi: 10.1073/pnas.86.7.2229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pierce G. F., Mustoe T. A., Senior R. M., Reed J., Griffin G. L., Thomason A., Deuel T. F. In vivo incisional wound healing augmented by platelet-derived growth factor and recombinant c-sis gene homodimeric proteins. J Exp Med. 1988 Mar 1;167(3):974–987. doi: 10.1084/jem.167.3.974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reed B. R., Clark R. A. Cutaneous tissue repair: practical implications of current knowledge. II. J Am Acad Dermatol. 1985 Dec;13(6):919–941. doi: 10.1016/s0190-9622(85)70242-3. [DOI] [PubMed] [Google Scholar]
- Rifkin D. B., Moscatelli D. Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol. 1989 Jul;109(1):1–6. doi: 10.1083/jcb.109.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shipley G. D., Keeble W. W., Hendrickson J. E., Coffey R. J., Jr, Pittelkow M. R. Growth of normal human keratinocytes and fibroblasts in serum-free medium is stimulated by acidic and basic fibroblast growth factor. J Cell Physiol. 1989 Mar;138(3):511–518. doi: 10.1002/jcp.1041380310. [DOI] [PubMed] [Google Scholar]
- Sporn M. B., Roberts A. B., Shull J. H., Smith J. M., Ward J. M., Sodek J. Polypeptide transforming growth factors isolated from bovine sources and used for wound healing in vivo. Science. 1983 Mar 18;219(4590):1329–1331. doi: 10.1126/science.6572416. [DOI] [PubMed] [Google Scholar]
- Sprugel K. H., McPherson J. M., Clowes A. W., Ross R. Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. Am J Pathol. 1987 Dec;129(3):601–613. [PMC free article] [PubMed] [Google Scholar]