The Contribution of Peroxisome Proliferator–Activated Receptor Gamma to Cutaneous Wound Healing

Leask, Andrew

doi:10.1089/wound.2012.0362

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…As a PPAR-γ agonist, PHR shows potential anti-inflammatory properties. In some studies, it is claimed that PPAR-γ plays a key role in suppressing the fibrogenic response by antagonizing TGF-β activity on wound healing [23]. In this study, we ascertained this claim to be the opposite and we observed that PHR led to a faster wound healing in diabetic conditions.…”

Section: Evaluation Of Wound Healing Abilitymentioning

confidence: 54%

Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study

Çam

Yildiz

Alenezi

et al. 2020

J. R. Soc. Interface.

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In order to provide more effective treatment strategies for the rapid healing of diabetic wounds, novel therapeutic approaches need to be developed. The therapeutic potential of peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist pioglitazone hydrochloride (PHR) in two different release kinetic scenarios, burst release and sustained release, was investigated and compared with in vitro and in vivo tests as potential wound healing dressings. PHR-loaded fibrous mats were successfully fabricated using polyvinyl-pyrrolidone and polycaprolactone by scalable pressurized gyration. The results indicated that PHR-loaded fibrous mats expedited diabetic wound healing in type-1 diabetic rats and did not show any cytotoxic effect on NIH/3T3 (mouse embryo fibroblast) cells, albeit with different release kinetics and efficacies. The wound healing effects of fibrous mats are presented with histological and biochemical evaluations. PHR-loaded fibrous mats improved neutrophil infiltration, oedema, and inflammation and increased epidermal regeneration and fibroblast proliferation, but the formation of hair follicles and completely improved oedema were observed only in the sustained release form. Thus, topical administration of PPAR-γ agonist in sustained release form has high potential for the treatment of diabetic wounds in inflammatory and proliferative phases of healing with high bioavailability and fewer systemic side effects.

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Section: Evaluation Of Wound Healing Abilitymentioning

confidence: 54%

Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study

Çam

Yildiz

Alenezi

et al. 2020

J. R. Soc. Interface.

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“…When the skin is disturbed due to injury, resident fibroblasts are submitted to mechanical stress. This stress, coupled with a TGF-β1 release from immune cells and platelets at the site of the wound, leads to the migration of dermal fibroblasts from normal surrounding skin near the site of injury [72]. Thus, fibroblasts differentiate into myofibroblasts.…”

Section: Pparγmentioning

confidence: 99%

TGF-β in fibrosis by acting as a conductor for contractile properties of myofibroblasts

2019

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Myofibroblasts are non-muscle contractile cells that play a key physiologically role in organs such as the stem villi of the human placenta during physiological pregnancy. They are able to contract and relax in response to changes in the volume of the intervillous chamber. Myofibroblasts have also been observed in several diseases and are involved in wound healing and the fibrotic processes affecting several organs, such as the liver, lungs, kidneys and heart. During the fibrotic process, tissue retraction rather than contraction is correlated with collagen synthesis in the extracellular matrix, leading to irreversible fibrosis and, finally, apoptosis of myofibroblasts. The molecular motor of myofibroblasts is the non-muscle type IIA and B myosin (NMMIIA and NMMIIB). Fibroblast differentiation into myofibroblasts is largely governed by the transforming growth factor-β1 (TGF-β1). This system controls the canonical WNT/β-catenin pathway in a positive manner, and PPARγ in a negative manner. The WNT/β-catenin pathway promotes fibrosis, while PPARγ prevents it. This review focuses on the contractile properties of myofibroblasts and the conductor, TGF-β1, which together control the opposing interplay between PPARγ and the canonical WNT/β-catenin pathway.

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“…The results of the present study showed that the topical application of CFE hydrogel induced a marked upregulation in the relative expression of the growth factors related to both angiogenesis, keratinocytes, fibroblast growth, and proliferation, which could be attributed to the increased expression of the glucagon-like peptides and their receptors, thus potentiating secretion of the growth factors such as vascular endothelial growth factors (VEGF) that improve wound microcirculation [ 47 ], epidermal growth factor (EPGF) [ 48 ], and fibroblast growth factors [ 49 ]. On the other hand, several previous reports illustrated the role of peroxisome proliferator-activated receptors alpha (PPAR-α) and their co-activators (PGC1-α) in the wound healing process [ 50 , 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria

et al. 2022

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Treatment of diabetic foot ulcer (DFU) is of great challenge as it is shown to be infected by multidrug resistant bacteria (MDR bacteria). Sixty four bacterial isolates were isolated from DFU cases; antibiotic susceptibility tests were carried out for all of them. One bacterial isolate (number 11) was shown to resist the action of 8 out of 12 antibiotics used and was identified by both a Vitek-2 system and 16S rRNA fingerprints as belonging to Proteus mirabilis, and was designated Proteus mirabilis LC587231 (P. mirabilis). Clove flower extract (CFE) inhibited distinctively the P. mirabilis bacterium obtained. GC-MS spectroscopy showed that this CFE contained nine bioactive compounds. The effect of CFE on wound healing of Type 1 diabetic albino rats (Rattus norvegicus) was studied. The results indicated that topical application of CFE hydrogel improved wound size, wound index, mRNA expression of the wound healing markers (Coli1, MMP9, Fibronectin, PCNA, and TGFβ), growth factor signaling pathways (PPAR-α, PGC1-α, GLP-1, GLPr-1, EGF-β, EGF-βr, VEGF-β, and FGF-β), inflammatory cytokine expression (IL8, TNFα, NFKβ, IL1β, and MCP1), as well as anti-inflammatory cytokines (IL4 & IL10), pro-apoptotic markers (FAS, FAS-L, BAX, BAX/BCL-2, Caspase-3, P53, P38), as well as an antiapoptotic one (BCL2). Furthermore, it improved the wound oxidative state and reduced the wound microbial load, as the cefepime therapy improved the wound healing parameters. Based on the previous notions, it could be concluded that CFE represents a valid antibiotics alternative for DFU therapy since it improves diabetic wound healing and exerts antibacterial activity either in vitro or in vivo.

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The Contribution of Peroxisome Proliferator–Activated Receptor Gamma to Cutaneous Wound Healing

Abstract: The development of drugs to control the rate of the fibroproliferative response are clinically relevant. Controlling PPAR-γ activity may be useful for prevention of scarring as well as for promoting the closure of chronic wounds.

Cited by 9 publications

References 32 publications

Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study

Evaluation of burst release and sustained release of pioglitazone-loaded fibrous mats on diabetic wound healing: an in vitro and in vivo comparison study

TGF-β in fibrosis by acting as a conductor for contractile properties of myofibroblasts

The Healing Capability of Clove Flower Extract (CFE) in Streptozotocin-Induced (STZ-Induced) Diabetic Rat Wounds Infected with Multidrug Resistant Bacteria

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