Regulation of Wound Healing by Growth Factors and Cytokines

Abstract

Werner, Sabine, and Richard Grose. Regulation of Wound Healing by Growth Factors and Cytokines. Physiol Rev 83: 835–870, 2003; 10.1152/physrev.00032.2002.—Cutaneous wound healing is a complex process involving blood clotting, inflammation, new tissue formation, and finally tissue remodeling. It is well described at the histological level, but the genes that regulate skin repair have only partially been identified. Many experimental and clinical studies have demonstrated varied, but in most cases beneficial, effects of exogenous growth factors on the healing process. However, the roles played by endogenous growth factors have remained largely unclear. Initial approaches at addressing this question focused on the expression analysis of various growth factors, cytokines, and their receptors in different wound models, with first functional data being obtained by applying neutralizing antibodies to wounds. During the past few years, the availability of genetically modified mice has allowed elucidation of the function of various genes in the healing process, and these studies have shed light onto the role of growth factors, cytokines, and their downstream effectors in wound repair. This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds. Most importantly, we also report on genetic studies addressing the functions of endogenous growth factors in the wound repair process.

Temporal Smad7 Transgene Induction in Mouse Epidermis Accelerates Skin Wound Healing

“…Since fibroblast activation and collagen production can be affected by keratinocyte-secreted factors and/or inflammation, 3,30 we examined whether keratinocyte-specific Smad7 induction affects type-I collagen production. In situ hybridization shows fewer COL1A1 mRNA-positive cells in the wound area of Smad7 tg skin compared to control skin wounds at days 5, 7, and 11 after wounding ( Figure 7A).…”

“…6 Reduced inflammation in Smad7 tg wounds could be responsible, at least in part, for reduced angiogenesis and collagen production, as both occurred after the re-duction in inflammation was first observed. Many inflammatory cytokines and chemokines are released by leukocytes, which are angiogenic and fibrogenic, 3,30 could be reduced in Smad7 wounds as a result of reduced leukocyte infiltration. As a result, early-stage angiogenesis and collagen production required for wound repair were not perturbed, whereas prolonged angiogenesis and collagen production were prevented in Smad7 tg wounds.…”

The use of autologous platelet–leukocyte gels to enhance the healing process in surgery, a review

“…It is generally accepted that platelet growth factors play a central role in the healing process and tissue formation [12]. Wound healing is a well-orchestrated and complex series of events involving cell-cell and cell-matrix interactions, in which platelet growth factors serve as messengers to regulate various processes.…”

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

“…14,15 TGF-␤ regulates a wide range of cellular processes, including cell proliferation, apoptosis, differentiation, migration, and ECM remodeling. 8,12,14,16 This multifunctionality allows TGF-␤ to participate in wound repair in multiple tissues and organs of the body. 12,17 Overexpression of TGF-␤ is often observed in in vivo wound sites.…”

“…8,12,14,16 This multifunctionality allows TGF-␤ to participate in wound repair in multiple tissues and organs of the body. 12,17 Overexpression of TGF-␤ is often observed in in vivo wound sites. 12 It is also present in several heart valverelated diseases (eg, calcific aortic stenosis, 18,19 mitral valve prolapse, 20,21 and Marfan syndrome).…”