Cytoskeleton responses in wound repair

Abreu-Blanco, María Teresa; Watts, James J.; Verboon, Jeffrey M.; Parkhurst, Susan M.

doi:10.1007/s00018-012-0928-2

Cited by 107 publications

(99 citation statements)

References 91 publications

(145 reference statements)

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“…Our results suggest that OA-induced EphB2 expression mediates the downstream signal pathways involved in the activation of Rac1; however, the precise mechanism requires further investigation. Furthermore, a cytoskeletal rearrangement accompanies stem cell migration to an injury site in response to wound-healing mediators such as proinflammatory cytokines, chemokines, and angiogenic factors [56,57]. We observed that an OA pretreatment improved the migration ability of UCB-MSCs and increased the number of UCB-MSCs at wound sites.…”

Section: Discussionmentioning

confidence: 85%

Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem cells through EphB2-dependent F-actin formation

Jung

Lee

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The role of unsaturated fatty acids (UFAs) is essential for determining stem cell functions. Eph/Ephrin interactions are important for regulation of stem cell fate and localization within their niche, which is significant for a wide range of stem cell behavior. Although oleic acid (OA) and Ephrin receptors (Ephs) have critical roles in the maintenance of stem cell functions, interrelation between Ephs and OA has not been explored. Therefore, the present study investigated the effect of OA-pretreated UCB-MSCs in skin wound-healing and underlying mechanism of Eph expression. OA promoted the motility of UCB-MSCs via EphB2 expression. OA-mediated GPR40 activation leads to Gαq-dependent PKCα phosphorylation. In addition, OA-induced phosphorylation of GSK3β was followed by β-catenin nuclear translocation in UCB-MSCs. Activation of β-catenin was blocked by PKC inhibitors, and OA-induced EphB2 expression was suppressed by β-cateninsiRNA transfection. Of those Rho-GTPases, Rac1 was activated in an EphB2-dependent manner. Accordingly, knocking down EphB2 suppressed F-actin expression. In vivo skin wound-healing assay revealed that OA-treated UCB-MSCs enhanced skin wound repair compared to UCB-MSCs pretreated with EphB2siRNA and OA. In conclusion, we showed that OA enhances UCB-MSC motility through EphB2-dependent F-actin formation involving PKCα/GSK3β/β-catenin and Rac1 signaling pathways.

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Section: Discussionmentioning

confidence: 85%

Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem cells through EphB2-dependent F-actin formation

Jung

Lee

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…16 GTPase activated Rho-associated coiled-coil kinases (ROCKs) are key regulators of cytoskeletal rearrangement through the regulation Lin11, Isl-1, Mec-3 (LIM) kinase/cofilin activity. 17 LIM domain proteins are also known to regulate transforming growth factor-β (TGF-β) signaling and affect EMT in wound healing.…”

Section: Introductionmentioning

confidence: 99%

ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in Human Embryonic Stem Cell–Derived Retinal Pigmented Epithelium

Croze

Thi

Clegg

2016

Trans. Vis. Sci. Tech.

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PurposeNonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD. However, the factors regulating RPE responses to AMD-associated lesions are not well understood. Here, we use cell culture to investigate the role of RhoA coiled coil kinases (ROCKs) in human embryonic stem cell–derived RPE (hESC-RPE) attachment, proliferation, and wound closure.MethodsH9 hESC were spontaneously differentiated into RPE cells. hESC-RPE cells were treated with a pan ROCK1/2 or a ROCK2 only inhibitor; attachment, and proliferation and cell size within an in vitro scratch assay were examined.ResultsPharmacological inhibition of ROCKs promoted hESC-RPE attachment and proliferation, and increased the rate of closure of in vitro wounds. ROCK inhibition decreased phosphorylation of cofilin and myosin light chain, suggesting that regulation of the cytoskeleton underlies the mechanism of action of ROCK inhibition.ConclusionsROCK inhibition promotes attachment, proliferation, and wound closure in H9 hESC-RPE cells. ROCK isoforms may have different roles in wound healing.Translational RelevanceModulation of the ROCK-cytoskeletal axis has potential in stimulating wound repair in transplanted RPE cells and attachment in cellular therapies.

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“…13,14,24 MT stabilizers, destabilizers, and motors are emerging as regulatory components of the migration machinery of cells. 9,25,26 A summary of key MRPs and their various functions is presented in Table 1.…”

mentioning

confidence: 99%

Targeting Microtubules for Wound Repair

Charafeddine

Nosanchuk

Sharp

2016

Advances in Wound Care

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Significance: Fast and seamless healing is essential for both deep and chronic wounds to restore the skin and protect the body from harmful pathogens. Thus, finding new targets that can both expedite and enhance the repair process without altering the upstream signaling milieu and causing serious side effects can improve the way we treat wounds. Since cell migration is key during the different stages of wound healing, it presents an ideal process and intracellular structural machineries to target. Recent Advances and Critical Issues: The microtubule (MT) cytoskeleton is rising as an important structural and functional regulator of wound healing. MTs have been reported to play different roles in the migration of the various cell types involved in wound healing. Specific microtubule regulatory proteins (MRPs) can be targeted to alter a section or subtype of the MT cytoskeleton and boost or hinder cell motility. However, inhibiting intracellular components can be challenging in vivo, especially using unstable molecules, such as small interfering RNA. Nanoparticles can be used to protect these unstable molecules and topically deliver them to the wound. Utilizing this approach, we recently showed that fidgetin-like 2, an uncharacterized MRP, can be targeted to enhance cell migration and wound healing. Future Directions: To harness the full potential of the current MRP therapeutic targets, studies should test them with different delivery platforms, dosages, and skin models. Screening for new MT effectors that boost cell migration in vivo would also help find new targets for skin repair.Keywords: microtubules, nanoparticle, siRNA, Fidgetin-like 2, cell migration SCOPE AND SIGNIFICANCEThis review explores the role of microtubules (MTs), a major component of the cell's internal skeleton, in wound healing, especially during cell migration. The structure and function of MTs are spatially and temporally regulated by microtubule regulatory proteins (MRPs), which have diverse effects on cell migration depending on their role and the cell type being targeted. The review also presents alternative techniques to identify and examine new therapeutic wound-healing targets. TRANSLATIONAL RELEVANCEWe recently characterized the role of fidgetin-like 2 (FL2), a novel MRP that can be targeted to enhance cell migration and healing both in vitro and in vivo wound-healing models. Identifying other MRPs that are involved in cell migration and wound healing !can elucidate how these proteins function and how they affect cell motility. As a faster and acute alternative to genetically modified animal models, RNA interference (RNAi) can be easily used to deplete these targets directly at the wound sites by utilizing nanotechnology and other technologies to deliver and protect small interfering RNA (siRNA). CLINICAL RELEVANCEBoth chronic and acute wounds are costly and painful medical issues

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Cytoskeleton responses in wound repair

Cited by 107 publications

References 91 publications

Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem cells through EphB2-dependent F-actin formation

Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem cells through EphB2-dependent F-actin formation

ROCK Inhibition Promotes Attachment, Proliferation, and Wound Closure in Human Embryonic Stem Cell–Derived Retinal Pigmented Epithelium

Targeting Microtubules for Wound Repair

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