Focal Contact and Hemidesmosomal Proteins in Keratinocyte Migration and Wound Repair

Hopkinson, Susan B.; Hamill, Kevin J.; Wu, Yvonne; Eisenberg, Jessica L.; Hiroyasu, Sho; Jones, Jonathan

doi:10.1089/wound.2013.0489

Cited by 63 publications

(60 citation statements)

References 147 publications

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“…We have attempted to assess whether this is the case by immunocytochemistry using antibodies against activated Rac1, but unfortunately without success. Regardless, we suggest that loss of β-PIX is likely to result in Rac1 mislocalization in keratinocytes since FAs and hemidesmosome protein complexes, both known to be Rac1 recruitment sites, show aberrant distributions as a consequence of β-PIX knockdown (Sehgal et al, 2006;Chang et al, 2007;Hamill et al, 2009;Hopkinson et al, 2014). Moreover, the potential importance of β-PIX in localizing Rac1 in keratinocytes is indicated by the inability of a SH3-mutant β-PIX to rescue processivity of keratinocytes exhibiting a loss in endogenous β-PIX since the SH3 mutant has been shown to be incapable of binding Rac1, in addition to PAK2 (Manser et al, 1998;ten Klooster et al, 2006).…”

Section: Discussionmentioning

confidence: 83%

“…Since the loss of β-PIX enhances the speed of HaCaT cells in both single cell and collective cell migration assays, we wondered what impact such deficiency has on keratinocyte FAs, the engine of their migration (Hopkinson et al, 2014). Antibodies against talin and paxillin show identical staining patterns in scratch-wounded monolayers of β-PIX KD HaCaT cells to control cells (Fig.…”

Section: Fa Size and Localization In β-Pix Kd Hacat Cellsmentioning

confidence: 92%

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Loss of β-PIX inhibits focal adhesion disassembly and promotes keratinocyte motility via myosin light chain activation

Hiroyasu

Stimac

Hopkinson

et al. 2017

Journal of Cell Science

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During healing of the skin, the cytoskeleton of keratinocytes and their matrix adhesions, including focal adhesions (FAs), undergo reorganization. These changes are coordinated by small GTPases and their regulators, including the guanine nucleotide exchange factor β-PIX (also known as ARHGEF7). In fibroblasts, β-PIX activates small GTPases, thereby enhancing migration. In keratinocytes in vitro, β-PIX localizes to FAs. To study β-PIX functions, we generated β-PIX knockdown keratinocytes. During wound closure of β-PIX knockdown cell monolayers, disassembly of FAs is impaired, and their number and size are increased. In addition, in the β-PIX knockdown cells, phosphorylated myosin light chain (MLC; also known as MYL2) is present not only in the leading edge of cells at the wound front, but also in the cells following the front, while p21-activated kinase 2 (PAK2), a regulator of MLC kinase (MYLK), is mislocalized. Inhibition or depletion of MYLK restores FA distribution in β-PIX knockdown cells. Traction forces generated by β-PIX knockdown cells are increased relative to those in control cells, a result consistent with an unexpected enhancement in the migration of single β-PIX knockdown cells and monolayers of such cells. We propose that targeting β-PIX might be a means of promoting epithelialization of wounds in vivo.

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Section: Discussionmentioning

confidence: 83%

Section: Fa Size and Localization In β-Pix Kd Hacat Cellsmentioning

confidence: 92%

Loss of β-PIX inhibits focal adhesion disassembly and promotes keratinocyte motility via myosin light chain activation

Hiroyasu

Stimac

Hopkinson

et al. 2017

Journal of Cell Science

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“…In any case, a role for a 6 b 4 in epidermal migration cannot yet be ruled out, since the severe epidermal blistering that occurs in a 6 b 4 -deficient mice presents a formidable challenge to wound healing experiments. More detailed discussions of potential roles for a 6 b 4 in keratinocyte migration can be found in separate reviews 8 (also, see the review by Hopkinson et al 117 in this issue).…”

Section: Autonomous Keratinocyte Functionsmentioning

confidence: 99%

Integrin Regulation of Epidermal Functions in Wounds

Longmate

DiPersio

2014

Advances in Wound Care

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“…Each phase requires coordinated effects of various cell types, including keratinocytes [4,5], fibroblasts [6], immune cells [7], etc., the disturbance of which in any phase leads to delayed cutaneous wound healing [8].…”

Section: Introductionmentioning

confidence: 99%

Estrogen Accelerates Cutaneous Wound Healing by Promoting Proliferation of Epidermal Keratinocytes via Erk/Akt Signaling Pathway

Zhou

Yang

Chen

et al. 2016

Cell Physiol Biochem

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Background: Previous studies have established that estrogen is capable of accelerating cutaneous wound healing through multiple mechanisms, one of which involves affecting keratinocytes biological properties, such as migration, proliferation, etc. This study aims to reveal the underlying molecular mechanisms of estrogen promoting epidermal keratinocytes proliferation. Method & Results: We found that compared with female mice with a normal estrous cycle, female mice with their ovaries removed before puberty exhibited a delayed cutaneous wound healing, thinner epidermis, and significantly fewer proliferating cell nuclear antigen (PCNA)-positive keratinocytes. Moreover, a significant increase in HaCaT proliferation was detected by a CCK8 assay when treated with 17 β-estradiol compared with those treated with control vehicle. Consistent with the results of the CCK8 assay, flow cytometry indicated a high proportion of 17 β-estradiol-treated HaCaT cells in S phase compared with vehicle-treated cells. Western blot analysis demonstrated the activation of Akt, Erk and upregulation of PCNA in HaCaT cells treated with 17 β-estradiol. Interestingly, Erk activation occurred prior to Akt activation. Upregulation of PCNA expression, elevated proliferation and high S phase fraction of HaCaT cell by 17 β-estradiol could be reversed by an Akt or Erk inhibitor. Moreover, Erk inhibition reversed 17 β-estradiol-induced Akt activation, whereas an Akt inhibitor exhibited no effect on Erk, further suggesting that Erk was on the upstream while Akt on the downstream of the signaling pathway. Conclusion: This study demonstrates that one of the critical mechanisms underlying 17 β-estradiol promoting skin wound healing is through regulation of keratinocyte proliferation via Erk/Akt signaling pathway.

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Focal Contact and Hemidesmosomal Proteins in Keratinocyte Migration and Wound Repair

Cited by 63 publications

References 147 publications

Loss of β-PIX inhibits focal adhesion disassembly and promotes keratinocyte motility via myosin light chain activation

Loss of β-PIX inhibits focal adhesion disassembly and promotes keratinocyte motility via myosin light chain activation

Integrin Regulation of Epidermal Functions in Wounds

Estrogen Accelerates Cutaneous Wound Healing by Promoting Proliferation of Epidermal Keratinocytes via Erk/Akt Signaling Pathway

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