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 proce...

/pdf/regulation-of-wound-healing-by-growth-factors-and-cytokines-2zk7orhjdk.pdf

Regulation of Wound Healing by Growth Factors and Cytokines

Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1524-475X.2008.00410.x

Growth factors and cytokines in wound healing.

Understanding wound healing today involves much more than simply stating that there are three phases: "inflammation, proliferation, and maturation." Wound healing is a complex series of reactions and interactions among cells and "mediators." Each year, new mediators are discovered and our understanding of inflammatory mediators and cellular interactions grows. This article will attempt to provide a concise report of the current literature on wound healing by first reviewing the phases of wound healing followed by "the players" of wound healing: inflammatory mediators (cytokines, growth factors, proteases, eicosanoids, kinins, and more), nitric oxide, and the cellular elements. The discussion will end with a pictorial essay summarizing the wound-healing process.

The basic science of wound healing.

Turnbull, Andrew V., and Catherine L. Rivier. Regulation of the Hypothalamic-Pituitary-Adrenal Axis by Cytokines: Actions and Mechanisms of Action. Physiol. Rev. 79: 1–71, 1999. — Glucocorticoids a...

Regulation of the Hypothalamic-Pituitary-Adrenal Axis by Cytokines: Actions and Mechanisms of Action

The role of vascular endothelial growth factor in wound healing.

In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica

In the present investigation the involvement of free radicals in a self-healing cutaneous wound has been demonstrated. The levels of different enzymatic and non-enzymatic antioxidants have been studied in 2,4,7 and 14 days old wounds and compared with normal skin. Except for glutathione reductase (GR), all other enzymatic and non-enzymatic antioxidants were found to decrease following wounding. The decrease was 60-70% in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) at 2, 4 and 7 days, while in the case of catalase (CAT) the decrease was 40-60% during this period. Although a complete recovery in the activity of CAT was observed, SOD and GPx did not recover completely and GST was found to be slightly elevated on 14th day post wounding. Non-enzymatic antioxidants viz, ascorbic acid, vitamin E and glutathione were also found to decrease to about 60-70% and except glutathione none of them was found to recover completely at 14th day postwounding. Interestingly thiobarbituric acid reactive substance (TBARS) expressed as malondialdehyde (MDA) equivalent, a marker of lipid peroxidation, decreased following wounding which could be because of meagre availability of lipid substrate and/or of ascorbic acid. The results indicate that wounding results in loss of different free radical scavengers both enzymatic and non-enzymatic which either partially or completely recover following healing.

Depletion of Reduced Glutathione, Ascorbic Acid, Vitamin E and Antioxidant Defence Enzymes in a Healing Cutaneous Wound

This investigation studied the contribution of antioxidants in delaying healing in excision cutaneous wounds (8 mm) in diabetic, aged and immunocompromised animals. Skin levels of catalase, glutathione (GSH), ascorbic acid (AA) and vitamin E in streptozotocin-induced diabetic rat were lower as compared to nondiabetics. The 7-d wound tissue of diabetic rats showed an increased vitamin E level along with depleted GSH content. In aged rats (18 months old), higher levels of skin superoxide dismutase (SOD), glutathione peroxidase (Gpx) and thiobarbituric acid reactive substances (TBARS) and lower levels of catalase and GSH were found as compared to their values in young rats (3-4 months old). The levels of SOD, GPx, catalase, AA, GSH and vitamin E in 7-d wound tissue of aged rats were significantly lower in comparison to those in young rats. However, TBARS were elevated in these wound tissues. The non-wounded skin of immunocompromised (athymic) mice showed lower levels of SOD, catalase, and TBARS and higher GSH and GPx levels in comparison to those present in normal mouse skin. Surprisingly, the analysis of 7-d wound tissue showed higher levels of SOD, catalase, GPx, and GSH and lower TBARS level in athymic mice compared to the wound tissue of normal mice. Thus low levels of antioxidants accompanied by raised levels of markers of free radical damage play a significant role in delaying wound healing in aged rats. In diabetic rats reduced glutathione levels may have a contributory role in delaying the healing process. However, in immunocompromised mice the antioxidant status following injury showed an adapted response.

Arti Shukla

Papers

In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica

Depletion of Reduced Glutathione, Ascorbic Acid, Vitamin E and Antioxidant Defence Enzymes in a Healing Cutaneous Wound

Antioxidant status in delayed healing type of wounds.

Healing potential of Calotropis procera on dermal wounds in Guinea pigs.

Differential Expression of Proteins during Healing of Cutaneous Wounds in Experimental Normal and Chronic Models