This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pierce, G. F. Articles by Thomason, A. Search for Related Content PubMed PubMed Citation Articles by Pierce, G. F. Articles by Thomason, A.

American Journal of Pathology, Vol 140, 1375-1388, Copyright © 1992 by American Society for Investigative Pathology

REGULAR ARTICLES

Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessation of repair

GF Pierce, JE Tarpley, D Yanagihara, TA Mustoe, GM Fox and A Thomason
Department of Experimental Pathology, Amgen Inc., Thousand Oaks, California 91320.

Recombinant platelet-derived growth factor (BB homodimer, rPDGF-BB), transforming growth factor beta 1 (rTGF-beta 1), and basic fibroblast growth factor (rbFGF) can accelerate healing of soft tissues. However, little information is available characterizing the components of wound matrix induced by these growth factors and the molecular mechanisms underlying accelerated repair and wound maturation. In this study, the composition, quantity, and rate of extracellular matrix deposition within growth factor-treated lapine ear excisional wounds were analyzed at different stages of healing using specific histochemical and immunohistochemical stains, coupled with image analysis techniques. Single application of optimal concentrations of each growth factor accelerated normal healing by 30% (P less than 0.0003); rPDGF-BB markedly augmented early glycosaminoglycan (GAG) and fibronectin deposition, but induced significantly greater levels of collagen later in the repair process, compared with untreated wounds rTGF-beta 1 treatment led to rapidly enhanced collagen synthesis and maturation, without increased GAG deposition. In contrast, rbFGF treatment induced a predominantly angiogenic response in wounds, with a marked increase in endothelia and neovessels (P less than 0.0001), and increased wound collagenolytic activity (P less than 0.03). rbFGF-treated wounds did not evolve into collagen-containing scars and continued to accumulate only provisional matrix well past wound closure. These results provide new evidence that growth factors influence wound repair via different mechanisms: 1) rPDGF-BB accelerates deposition of provisional wound matrix; 2) rTGF-beta 1 accelerates deposition and maturation of collagen; and 3) rbFGF induces a profound monocellular angiogenic response which may lead to a marked delay in wound maturation, and the possible loss of the normal signal(s) required to stop repair. These results suggest that specific growth factors may selectively regulate components of the repair response by differing mechanisms, offering the potential for targeted therapeutic intervention.

This article has been cited by other articles:

				T. Yukami, M. Hasegawa, Y. Matsushita, T. Fujita, T. Matsushita, M. Horikawa, K. Komura, K. Yanaba, Y. Hamaguchi, T. Nagaoka, et al. Endothelial selectins regulate skin wound healing in cooperation with L-selectin and ICAM-1 J. Leukoc. Biol., September 1, 2007; 82(3): 519 - 531. [Abstract] [Full Text] [PDF]

				Y. Zhao, T. Shimizu, J. Nishihira, Y. Koyama, T. Kushibiki, A. Honda, H. Watanabe, R. Abe, Y. Tabata, and H. Shimizu Tissue Regeneration Using Macrophage Migration Inhibitory Factor-Impregnated Gelatin Microbeads in Cutaneous Wounds Am. J. Pathol., December 1, 2005; 167(6): 1519 - 1529. [Abstract] [Full Text] [PDF]

				N. E. CARLSON and R. B. ROACH JR. Platelet-rich plasma: Clinical applications in dentistry J Am Dent Assoc, October 1, 2002; 133(10): 1383 - 1386. [Abstract] [Full Text] [PDF]

				H. Zhang and A. C. Issekutz Growth factor regulation of neutrophil-endothelial cell interactions J. Leukoc. Biol., August 1, 2001; 70(2): 225 - 232. [Abstract] [Full Text] [PDF]

				G. F. Pierce Inflammation in Nonhealing Diabetic Wounds : The Space-Time Continuum Does Matter Am. J. Pathol., August 1, 2001; 159(2): 399 - 403. [Full Text]

				S. R. Bonomo, J. D. Davidson, J. W. Tyrone, X. Lin, and T. A. Mustoe Enhancement of Wound Healing by Hyperbaric Oxygen and Transforming Growth Factor {beta}3 in a New Chronic Wound Model in Aged Rabbits Arch Surg, October 1, 2000; 135(10): 1148 - 1153. [Abstract] [Full Text] [PDF]

				T. Nagaoka, Y. Kaburagi, Y. Hamaguchi, M. Hasegawa, K. Takehara, D. A. Steeber, T. F. Tedder, and S. Sato Delayed Wound Healing in the Absence of Intercellular Adhesion Molecule-1 or L-Selectin Expression Am. J. Pathol., July 1, 2000; 157(1): 237 - 247. [Abstract] [Full Text] [PDF]

				H. HAMADA, V. VALLYATHAN, C. D. COOL, E. BARKER, Y. INOUE, and L. S. NEWMAN Mast Cell Basic Fibroblast Growth Factor in Silicosis Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 2026 - 2034. [Abstract] [Full Text]

				T. E. Rayner, A. J. Cowin, J. G. Robertson, R. D. Cooter, R. C. Harries, G. O. Regester, G. W. Smithers, C. Goddard, and D. A. Belford Mitogenic whey extract stimulates wound repair activity in vitro and promotes healing of rat incisional wounds Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1651 - R1660. [Abstract] [Full Text] [PDF]

				E. A. Chen, L. Zhao, M. Bamat, R. von Borstel, and T. Mustoe Acceleration of Wound Healing With Topically Applied Deoxyribonucleosides Arch Surg, May 1, 1999; 134(5): 520 - 525. [Abstract] [Full Text] [PDF]

				C. J. Corral, A. Siddiqui, L. Wu, C. L. Farrell, D. Lyons, and T. A. Mustoe Vascular Endothelial Growth Factor Is More Important Than Basic Fibroblastic Growth Factor During Ischemic Wound Healing Arch Surg, February 1, 1999; 134(2): 200 - 205. [Abstract] [Full Text] [PDF]

				L. Wu, Y.-P. Xia, S. I. Roth, E. Gruskin, and T. A. Mustoe Transforming Growth Factor-ß1 Fails to Stimulate Wound Healing and Impairs Its Signal Transduction in an Aged Ischemic Ulcer Model : Importance of Oxygen and Age Am. J. Pathol., January 1, 1999; 154(1): 301 - 309. [Abstract] [Full Text] [PDF]

				J. Liu, D. Fitzli, M. Liu, I. Tseu, I. Caniggia, D. Rotin, and M. Post PDGF-induced glycosaminoglycan synthesis is mediated via phosphatidylinositol 3-kinase Am J Physiol Lung Cell Mol Physiol, May 1, 1998; 274(5): L702 - L713. [Abstract] [Full Text] [PDF]

				W. Casscells Growth Factor Therapies for Vascular Injury and Ischemia Circulation, June 1, 1995; 91(11): 2699 - 2702. [Full Text]

				M. Papetti and I. M. Herman Mechanisms of normal and tumor-derived angiogenesis Am J Physiol Cell Physiol, May 1, 2002; 282(5): C947 - C970. [Abstract] [Full Text] [PDF]