Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression.
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.
Tkalcević
Vanesa Ivetić
VI
PLIVA Research Institute Ltd, Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia.
Cuzić
Snjezana
S
Brajsa
Karmen
K
Mildner
Boris
B
Bokulić
Ana
A
Situm
Kristina
K
Perović
Daniela
D
Glojnarić
Ines
I
Parnham
Michael J
MJ
D000818:Animals; D000077214:Becaplermin; D018938:Caco-2 Cells; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D006097:Granulation Tissue / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015745:Granuloma, Foreign-Body / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects*
D016207:Cytokines; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C491000:NAB2 protein, human; D010446:Peptide Fragments; D010982:Platelet-Derived Growth Factor; D011506:Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D000077214:Becaplermin; C083833:BPC 157; D003094:Collagen