FOXO1 differentially regulates both normal and diabetic wound healing

Zhang, Chenying; Ponugoti, Bhaskar; Tian, Chen; Xu, Fanxing; Tarapore, Rohinton; Batres, Angelika; Alsadun, Sarah; Lim, Jason; Dong, Guofa; Graves, Dana T.

doi:10.1084/jem.2125oia30

Cited by 5 publications

(11 citation statements)

References 21 publications

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“…Additionally, hyperglycemia induced AGE formation and increased levels of TNF-α disrupts FOXO1 interaction with TGF-β1, thus preventing FOXO1 from inducing TGF-β1 transcription. These studies reveal the negative side of TGF-β1 in the healing process, resulting in impaired healing (Zhang et al 2015).…”

Section: Role Of Foxo In Wound Healingmentioning

confidence: 84%

“…Restoration of damaged tissue requires stimulatory and inhibitory mediators. FOXO transcription factors (homeostatic factors) are involved in regulating wound healing and tissue regeneration, however their exact function is not fully understood (Roupe et al 2014;Shaklai et al 2015;Zhang et al 2015). Mori et al, reported that in a murine skin injury model there is elevated mRNA expression and nuclear localization of FOXO1 and FOXO3.…”

Section: Role Of Foxo In Wound Healingmentioning

confidence: 99%

“…Other studies have recently reported that scalp wound healing is impaired in FOXO1 ± genetic mice with reduced re-epithelialization (Ponugoti et al 2013). In diabetic mice, the conditional deletion of FOXO1 has a positive effect, with enhanced wound closure as compared with normal wounds (Zhang et al 2015;Xu et al 2015). In order to determine the differential effect of FOXO1 under hyperglycemic conditions, mRNA profiling was carried out in diabetic mice.…”

Section: Role Of Foxo In Wound Healingmentioning

confidence: 99%

“…It was established that FOXO1 upregulates genes such as chemokine ligand 20 (CCL20), serpin peptidase inhibitor clade B2 (SERPINB2), and interleukin-36γ (IL-36γ). Furthermore, in DM, unfavorable conditions such as hyperglycemia, AGEs and increased expression of TNF-α stimulates FOXO1 binding to the promoter site of these genes to increase their expression (Zhang et al 2015). Elevated levels of CCL20, SERPINB2, and IL-36γ inhibits keratinocyte migration and reduces re-epithelization, thereby a delay in healing is observed (Xu et al 2015).…”

Section: Role Of Foxo In Wound Healingmentioning

confidence: 99%

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Understanding the perspectives of forkhead transcription factors in delayed wound healing

Rajendran

Kumar

Houreld

et al. 2018

J. Cell Commun. Signal.

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Wound healing is a complex overlapping biological process that involves a sequence of events coordinated by various cells, proteins, growth factors, cytokines and signaling molecules. Recent evidence indicates that forkhead box O1 (FOXO1) transcription factors play an important role in organizing these events to stimulate wound healing. The ubiquitously expressed forkhead box, class O (FOXO) transcription factors act as cell signaling molecules in various transcriptional processes that are involved in diverse cellular activities, including cell death, cell differentiation, DNA repair, apoptosis, and oxidative stress in response to stimuli, and interact with numerous proteins. Due to the activation of FOXO targeted genes, FOXOs are involved in maintaining the balance between oxidative stress and antioxidants. In humans, different isoforms of FOXO namely FOXO1, FOXO3, FOXO4 and FOXO6 are present, however only FOXO1 and FOXO3 possess biological functions such as morphogenesis, maintenance and tissue regeneration. This might make FOXOs an important therapeutic target to enhance wound healing in diabetes, and to avoid over scarring. In spite of extensive literature, little is known regarding the role of FOXO and its relationship in wound healing. This review provides a summary of FOXO proteins and their biological role in wound healing and oxidative stress.

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Section: Role Of Foxo In Wound Healingmentioning

confidence: 84%

Section: Role Of Foxo In Wound Healingmentioning

confidence: 99%

Section: Role Of Foxo In Wound Healingmentioning

confidence: 99%

Section: Role Of Foxo In Wound Healingmentioning

confidence: 99%

See 2 more Smart Citations

Understanding the perspectives of forkhead transcription factors in delayed wound healing

Rajendran

Kumar

Houreld

et al. 2018

J. Cell Commun. Signal.

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“…Conditional deletion of FOXO1 in keratinocytes of diabetic wounds has the opposite effect compared with its role in normal healing (Xu et al 2015;Zhang et al 2015). Deleting FOXO1 in keratinocytes in oral mucosal wounds or in skin wounds significantly improves re-epithelialization.…”

mentioning

confidence: 99%

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

Xiao

Graves

2015

J Dent Res

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SerpinB2 Deficiency Results in a Stratum Corneum Defect and Increased Sensitivity to Topically Applied Inflammatory Agents

Schroder

Anraku

et al. 2016

The American Journal of Pathology

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SerpinB2 (plasminogen activator inhibitor type 2) is constitutively expressed at high levels by differentiating keratinocytes in mice and humans; however, the physiological function of keratinocyte SerpinB2 remains unclear. Herein, we show that SerpinB2(-/-) mice are more susceptible to contact dermatitis after topical application of dinitrofluorobenzene, and show enhanced inflammatory lesions after topical applications of phorbol ester. Untreated SerpinB2(-/-) mice showed no overt changes in epithelial structure, and we were unable to find evidence for a role for keratinocyte SerpinB2 in regulating immunity, apoptosis, IL-1β production, proteasomal activity, or wound healing. Instead, the phenotype was associated with impaired skin barrier function and a defective stratum corneum, with SerpinB2(-/-) mice showing increased transepidermal water loss, increased overt loss of stratum corneum in inflammatory lesions, and impaired stratum corneum thickening after phorbol ester treatment. Immunoblotting suggested that SerpinB2 (cross-linked into the cornified envelope) is present in the stratum corneum and retains the ability to form covalent inhibitory complexes with urokinase. Data suggest that the function of keratinocyte SerpinB2 is protection of the stratum corneum from proteolysis via inhibition of urokinase, thereby maintaining the integrity and barrier function of the stratum corneum, particularly during times of skin inflammation. Implications for studies involving genetically modified mice treated with topical agents and human dermatological conditions, such as contact dermatitis, are discussed.

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FOXO1 differentially regulates both normal and diabetic wound healing

Cited by 5 publications

References 21 publications

Understanding the perspectives of forkhead transcription factors in delayed wound healing

Understanding the perspectives of forkhead transcription factors in delayed wound healing

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

SerpinB2 Deficiency Results in a Stratum Corneum Defect and Increased Sensitivity to Topically Applied Inflammatory Agents

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