Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression

PLIVA Research Institute Ltd, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia.
European Journal of Pharmacology (Impact Factor: 2.68). 10/2007; 570(1-3):212-21. DOI: 10.1016/j.ejphar.2007.05.072
Source: PubMed

ABSTRACT Apart from becaplermin (recombinant human platelet-derived growth factor homodimer of B chains, PDGF-BB), for the treatment of lower extremity diabetic ulcers, few agents are available for pharmacological stimulation of wound healing. We have compared the mechanism of action of the potential wound healing agent, PL 14736 (G E P P P G K P A D D A G L V), with that of PDGF-BB on granulation tissue formation following sponge implantation in the normoglycemic rat and in healing full-thickness excisional wounds in db/db genetically diabetic mice. Expression of the immediate response gene, early growth response gene-1 (egr-1) was studied in Caco-2 cells in vitro. While PDGF-BB and PL 14736 had similar selectivity for stimulation of granulation tissue in both sponge granuloma and in healing wounds in db/db mice, PL 14736 was more active in stimulating early collagen organization. It also stimulated expression of egr-1 and its repressor nerve growth factor 1-A binding protein-2 (nab2) in non-differentiated Caco-2 cells more rapidly than PDGF-BB. EGR-1 induces cytokine and growth factor generation and early extracellular matrix (collagen) formation, offering an explanation for the beneficial effects of PL 14736 on wound healing.

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    • "There are some other points which should also be mentioned. For instance, besides stimulating the expression of the early growth response 1 (egr-1) gene [108], responsible for collagen and blood vessel formation, BPC 157 has been shown to stimulate the expression of the egr-1 repressor nerve growth factor 1-A binding protein-2 (nab2) [108]. Therefore, it is possible that BPC 157 and nab2 [109] are part of a feedback mechanism that serves to regulate egr-1-mediated gene transcription and that this may be an effective axis in BPC 157 healing potential . "
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