Enhancement by PL 14736 of granulation and collagen organization in healing wounds and the potential role of egr-1 expression
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.
- SourceAvailable from: Jelena Suran
[Show abstract] [Hide abstract]
- "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 , 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) . Therefore, it is possible that BPC 157 and nab2  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 . "
ABSTRACT: Stable gastric pentadecapeptide BPC 157 is an anti-ulcer peptidergic agent, proven in clinical trials to be both safe in inflammatory bowel disease (PL-10, PLD-116, PL 14736) and wound healing, stable in human gastric juice, with no toxicity being reported. Recently, we claim that BPC 157 may be used as an antidote against NSAIDs. We focused on BPC 157 beneficial effects on stomach, duodenum, intestine, liver and brain injuries, adjuvant arthritis, pain, hyper/hypothermia, obstructive thrombus formation and thrombolysis, blood vessel function, counteraction of prolonged bleeding and thrombocytopenia after application of various anticoagulants and anti-platelet agents and wound healing improvement. The arguments for BPC 157 antidote activity (i.e., the role of BPC 157 in cytoprotection, being a novel mediator of Roberts cytoprotection and BPC 157 beneficial effects on NSAID mediated lesions in the gastrointestinal tract, liver and brain and finally, counteraction of aspirin-induced prolonged bleeding and thrombocytopenia) obviously have a counteracting effect on several established side-effects of NSAID use. The mentioned variety of the beneficial effects portrayed by BPC 157 may well be a foundation for establishing BPC 157 as a NSAID antidote since no other single agent has portrayed a similar array of effects. Unlike NSAIDs, a very high safety (no reported toxicity (LD1 could be not achieved)) profile is reported for BPC 157. Also, unlike the different dosage levels of aspirin, as a NSAID prototype, which differ by a factor of about ten, all these beneficial and counteracting effects of BPC 157 were obtained using the equipotent dosage (µg, ng/kg) in parenteral or peroral regimens.Current pharmaceutical design 08/2012; 19(1). DOI:10.2174/13816128130111 · 3.29 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The Association for Neurophyschopharmacology hosted a satellite meeting as part of the 14th Annual Meeting of the Psychoneuroimmunology Research Society. The meeting was entitled 'Cytokines and Depression III: Identification and Treatment of Symptoms Associated with Inflammation in Diseases with Inflammation in Medically Ill Patients' and was held in Bordeaux, France on 28 - 29 May, 2007. The meeting comprised approximately 40 participants from many leading laboratories and hospitals from around the world looking to understand some of the clinical issues associated with depression and behavioural changes, with the aims of exploring better ways of clinical monitoring and marshalling drug discovery efforts from bespoke and alternate indications in providing new therapeutic approaches.Expert Opinion on Investigational Drugs 11/2007; 16(10):1725-34. DOI:10.1517/13543722.214.171.1245 · 5.43 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Stable gastric pentadecapeptide BPC 157 accelerates the healing of a transected Achilles tendon and a transected quadriceps muscle. It may also be of clinical relevance as a systemic and local peptide treatment for crush injury of a major muscle, such as gastrocnemius muscle complex. BPC 157 is effective without a carrier, and it is presently undergoing trials for inflammatory bowel disease, and no toxicity has so far been reported. In crushed rats (force delivered 0.727 Ns/cm2), BPC 157 was applied either intraperitoneally or locally, as a thin cream layer, immediately after injury (sacrifice at 2 h), and once a day for 14 days. BPC 157 improved muscle healing, macroscopically (less hematoma and edema, no post-injury leg contracture), microscopically, functionally, and also based on enzyme activity (creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase). BPC 157, at all investigated intervals, given locally or intraperitoneally, accelerated post-injury muscle healing and also helped to restore the full function.Surgery Today 02/2008; 38(8):716-25. DOI:10.1007/s00595-007-3706-2 · 1.21 Impact Factor