Downregulation of PTEN at Corneal Wound Sites Accelerates Wound Healing through Increased Cell Migration

Cao, Lin; Graue-Hernández, Enrique O; Tran, Vu; Reid, Brian; Pu, Jun; Mannis, Mark J.; Zhao, Min

doi:10.1167/iovs.10-5972

Cited by 38 publications

(39 citation statements)

References 35 publications

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“…PTEN expression was prominent in axons but expressed in other cell types, where it may impose similar barriers to cell migration and plasticity during normal skin remodeling or after wound repair. For example, PTEN inhibition enhances corneal wound healing [34]. Similar barriers may be erected by RHOA [15], also upregulated in the wounds we analyzed and known to interact with PTEN [35].…”

Section: Discussionmentioning

confidence: 99%

Loss of Innervation and Axon Plasticity Accompanies Impaired Diabetic Wound Healing

et al. 2013

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Loss of cutaneous innervation from sensory neuropathy is included among mechanisms for impaired healing of diabetic skin wounds. The relationships between cutaneous axons and their local microenvironment during wound healing are challenged in diabetes. Here, we show that secondary wound closure of the hairy dorsal skin of mice is delayed by diabetes and is associated with not only a pre-existing loss of cutaneous axons but substantial retraction of axons around the wound. At 7d following a 3mm punch wound, a critical period of healing and reinnervation, both intact skin nearby the wound and skin directly at the wound margins had over 30-50% fewer axons and a larger deficit of ingrowing axons in diabetics. These findings contrasted with a pre-existing 10-15% deficit in axons. Moreover, new diabetic ingrowing axons had less evidence of plasticity. Unexpectedly, hair follicles adjacent to the wounds had a 70% reduction in their innervation associated with depleted expression of hair follicular stem cell markers. These impairments were associated with the local upregulation of two established axon regenerative ‘roadblocks’: PTEN and RHOA, potential but thus far unexplored mediators of these changes. The overall findings identify striking and unexpected superimposed cutaneous axon loss or retraction beyond that expected of diabetic neuropathy alone, associated with experimental diabetic skin wounding, a finding that prompts new considerations in diabetic wounds.

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Section: Discussionmentioning

confidence: 99%

Loss of Innervation and Axon Plasticity Accompanies Impaired Diabetic Wound Healing

et al. 2013

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“…When PI3K is activated, membrane protrusion and lamellipodia formation is initiated at that site, facilitating directed migration toward the cathode. Pharmacological inhibition of PI3K activity or selective disruption of the PI3K-γ isoform has been shown to block electrotaxis in wound healing assays and organ cultures [98,99]. Furthermore, in keratinocytes, deletion of phosphatase and tensin homolog (PTEN), a phosphatase that functions as a negative regulator of PI3K, resulted in increased Akt phosphorylation and enhanced electrotaxis.…”

Section: Electrotaxismentioning

confidence: 99%

CFTR Involvement in Cell Migration and Epithelial Restitution

O’Grady¹

2017

Progress in Understanding Cystic Fibrosis

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Over the past decade, research has shown that cystic fibrosis transmembrane conductance regulator (CFTR) plays an important role in epithelial cell migration and wound healing. Experiments with airway epithelium, ovarian epithelial cells, placental epithelium and epidermal keratinocytes demonstrated that CFTR function is necessary to achieve maximum migration rates during restitution and in certain cancer cells, CFTR activity contributes to tumor cell invasion. Multiple mechanisms appear to underlie the motility-promoting actions of CFTR, and although many details remain to be established, our present understanding indicates that processes such as electrotaxis (galvanotaxis), integrin-mediated cell adhesion and lamellipodia protrusion are dependent on normal CFTR function. In this chapter, the role of CFTR in epithelial cell migration and its implications in cystic fibrosis (CF) will be reviewed with emphasis on the underlying mechanisms that may explain observations made in various epithelial tissues, particularly in airways. Ultimately, a better understanding of CFTR involvement in epithelial repair may lead to new therapeutic approaches to improve barrier function and reduce airway infection and inflammation associated with CF.

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“…It also plays a role in wound healing [42], leukemia therapy [43], and cardioprotection [44], [45]. Thus, PTEN is key point in many human diseases.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Decreases Rat Cortical Neuron Injury and Blood-Brain Barrier Permeability, and Improves Neurological Functional Recovery in Traumatic Brain Injury Model

et al. 2013

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Background and PurposeRecent evidence has supported the neuroprotective effect of bpV (pic), an inhibitor of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in models of ischemic stroke. However, whether PTEN inhibitors improve long-term functional recovery after traumatic brain injury (TBI) and whether PTEN affects blood brain barrier (BBB) permeability need further elucidation. The present study was performed to address these issues.MethodsAdult Sprague-Dawley rats were subjected to fluid percussion injury (FPI) after treatment with a well-established PTEN inhibitor bpV (pic) or saline starting 24 h before FPI. Western blotting, real-time quantitative PCR, or immunostaining was used to measure PTEN, p-Akt, or MMP-9 expression. We determined the presence of neuron apoptosis by TUNEL assay. Evans Blue dye extravasation was measured to evaluate the extent of BBB disruption. Functional recovery was assessed by the neurological severity score (NSS), and Kaplan-Meier analysis was used for survival analysis.ResultsPTEN expression was up-regulated after TBI. After bpV (pic) treatment, p-Akt was also up-regulated. We found that bpV (pic) significantly decreased BBB permeability and reduced the number of TUNEL-positive cells. We further demonstrated that PTEN inhibition improved neurological function recovery in the early stage after TBI.ConclusionThese data suggest that treatment with the PTEN inhibitor bpV (pic) has a neuroprotective effect in TBI rats.

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Downregulation of PTEN at Corneal Wound Sites Accelerates Wound Healing through Increased Cell Migration

Cited by 38 publications

References 35 publications

Loss of Innervation and Axon Plasticity Accompanies Impaired Diabetic Wound Healing

Loss of Innervation and Axon Plasticity Accompanies Impaired Diabetic Wound Healing

CFTR Involvement in Cell Migration and Epithelial Restitution

Inhibition of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Decreases Rat Cortical Neuron Injury and Blood-Brain Barrier Permeability, and Improves Neurological Functional Recovery in Traumatic Brain Injury Model

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