FOXO1 promotes wound healing through the up-regulation of TGF-β1 and prevention of oxidative stress

Ponugoti, Bhaskar; Xu, Fanxing; Zhang, Chenying; Tian, Chen; Pacios, Sandra; Graves, Dana T.

doi:10.1083/jcb.201305074

Cited by 150 publications

(174 citation statements)

References 51 publications

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“…It was reported that TGF-β1 and MMP-9 were involved in keratinocyte migration. [25][26][27] The results indicated that the Col/BG nanofibers not only promoted the adhesion and proliferation (P,0.05) of HaCaTs ( Figure 3A-C), but also could upregulate the expression of MMP-9 and TGF-β1 genes ( Figure 3D, P,0.05), which may be beneficial for HaCaTs migration.…”

Section: Adhesion and Migration Of Hacats Induced By The Col/bg Nanofmentioning

confidence: 99%

Multifunctional and biomimetic fish collagen/bioactive glass nanofibers: fabrication, antibacterial activity and inducing skin regeneration in vitro and in vivo

Zhou¹,

Sui²,

Mo³

et al. 2017

IJN

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The development of skin wound dressings with excellent properties has always been an important challenge in the field of biomedicine. In this study, biomimetic electrospun fish collagen/bioactive glass (Col/BG) nanofibers were prepared. Their structure, tensile strength, antibacterial activity and biological effects on human keratinocytes, human dermal fibroblasts and human vascular endothelial cells were investigated. Furthermore, the Sprague Dawley rat skin defect model was used to validate their effect on wound healing. The results showed that compared with pure fish collagen nanofibers, the tensile strength of the Col/BG nanofibers increased to 21.87±0.21 Mpa, with a certain degree of antibacterial activity against Staphylococcus aureus . It was also found that the Col/BG nanofibers promoted the adhesion, proliferation and migration of human keratinocytes. Col/BG nanofibers induced the secretion of type one collagen and vascular endothelial growth factor by human dermal fibroblasts, which further stimulated the proliferation of human vascular endothelial cells. Animal experimentation indicated that the Col/BG nanofibers could accelerate rat skin wound healing. This study developed a type of multifunctional and biomimetic fish Col/BG nanofibers, which had the ability to induce skin regeneration with adequate tensile strength and antibacterial activity. The Col/BG nanofibers are also easily available and inexpensive, providing the possibility for using as a functional skin wound dressing.

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Section: Adhesion and Migration Of Hacats Induced By The Col/bg Nanofmentioning

confidence: 99%

Multifunctional and biomimetic fish collagen/bioactive glass nanofibers: fabrication, antibacterial activity and inducing skin regeneration in vitro and in vivo

Zhou¹,

Sui²,

Mo³

et al. 2017

IJN

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“…60 Moreover, FOXO1 reduces oxidative stress in keratinocytes preventing apoptosis and facilitating wound healing (Fig. 3B).…”

Section: Advances In Regulation Of Mmps Signal Transduction Mechanismmentioning

confidence: 99%

Metalloproteinases and Wound Healing

Caley¹,

Martins²,

O’Toole³

2015

Advances in Wound Care

673

503

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Significance: Matrix metalloproteinases (MMPs) are present in both acute and chronic wounds. They play a pivotal role, with their inhibitors, in regulating extracellular matrix degradation and deposition that is essential for wound reepithelialization. The excess protease activity can lead to a chronic nonhealing wound. The timed expression and activation of MMPs in response to wounding are vital for successful wound healing. MMPs are grouped into eight families and display extensive homology within these families. This homology leads in part to the initial failure of MMP inhibitors in clinical trials and the development of alternative methods for modulating the MMP activity. MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation. Recent Advances: Recent research has identified several new MMP modulators, including photodynamic therapy, protease-absorbing dressing, microRNA regulation, signaling molecules, and peptides. Critical Issues: Wound healing requires the controlled activity of MMPs at all stages of the wound healing process. The loss of MMP regulation is a characteristic of chronic wounds and contributes to the failure to heal. Future Directions: Further research into how MMPs are regulated should allow the development of novel treatments for wound healing. SCOPE AND SIGNIFICANCEThis review highlights recent advances in understanding the regulation of matrix metalloproteinases (MMPs) in skin and how this knowledge might be applied in patients to improve wound healing. Selected recent advances include microRNA (MiR) regulation, novel peptides, signal transduction, experimental therapies, and novel dressings. TRANSLATIONAL RELEVANCEWound healing is a complex multicellular process involving fibroblasts, keratinocytes, and endothelial cells as well as inflammatory cells. The healing process follows an orderly sequence of events incorporating four distinct, yet overlapping, phases: hemostasis, the inflammatory phase, the proliferation phase, and the remodeling phase. The phases of wound healing are regulated by cross talk between different groups of molecules, including extracellular matrix (ECM), integrins, growth factors, and MMPs. Migration of cells on ECM, and remodeling and degradation of the ECM by MMPs are key elements of wound repair. CLINICAL RELEVANCEChronic wounds, including pressure sores, venous ulcers, and diabetic ulcers, are a major clinical problem with considerable morbidity and associated financial costs. Excessive MMPs are a feature of chronic wounds. Regulation of MMP levels in wounds could lead to improved wound healing. OVERVIEWThe MMP family is a group of calcium-dependent zinc-containing enzymes that are involved in the degradation of ECM. Family members share structural ( Fig. 1) and sequence similarities, a flexible proline-rich hinge region, and a hemopexinlike C-terminal domain, which functions in recognition of substrates (usually ECM). Excep...

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“…FOXO1 promotes keratinocytes migration by upregulating transforming growth factor β1 (TGF-β1) and its downstream target genes: integrin α3 and ß6 and matrix metalloproteinase 3 and 9. FOXO1 activation is also important for resisting oxidative stress that would otherwise interfere with keratinocyte migration and stimulate apoptosis (Ponugoti et al 2013). Similarly, in oral mucosa, deletion of FOXO1 in keratinocytes results in reduced TGF-β1 expression, diminished mucosal epithelial migration, and impaired re-epithelialization .…”

Section: Perspectivementioning

confidence: 99%

“…FOXO1 belongs to a family of forkhead transcription factors that participate in a wide range of cellular processes, including cell cycle arrest, DNA repair, apoptosis, and oxidative stress resistance. Ponugoti et al (2013) showed that FOXO1 nuclear localization increased 4-fold in wound-healing keratinocytes. FOXO1 promotes keratinocytes migration by upregulating transforming growth factor β1 (TGF-β1) and its downstream target genes: integrin α3 and ß6 and matrix metalloproteinase 3 and 9.…”

Section: Perspectivementioning

confidence: 99%

Impact of Diabetes on the Protective Role of FOXO1 in Wound Healing

Xiao

Graves

2015

J Dent Res

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FOXO1 promotes wound healing through the up-regulation of TGF-β1 and prevention of oxidative stress

Abstract: FOXO1 orchestrates wound healing through the up-regulation of TGF-β1 and protection against oxidative stress, which together act to promote keratinocyte migration and decrease apoptosis.

Cited by 150 publications

References 51 publications

Multifunctional and biomimetic fish collagen/bioactive glass nanofibers: fabrication, antibacterial activity and inducing skin regeneration in vitro and in vivo

Multifunctional and biomimetic fish collagen/bioactive glass nanofibers: fabrication, antibacterial activity and inducing skin regeneration in vitro and in vivo

Metalloproteinases and Wound Healing

Impact of Diabetes on the Protective Role of FOXO1 in Wound Healing

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