Pigment epithelium-derived factor plays an inhibitory role in proliferation and migration of HaCaT cells

Li, Chunming; Li, Wei; Man, Xiao‐Yong; Zhou, Jiong; Chen, Jiaqi; Cai, Sheng; Zheng, Min

doi:10.1007/s11033-010-0336-3

Cited by 13 publications

(14 citation statements)

References 23 publications

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“…PEDF has previously been shown to inhibit migration and proliferation in the human keratinocyte cell line HaCAT (15) and in endothelial cells (1); therefore, we wondered if PEDF would have similar effects on primary NHEK. Using a scratch wound assay on a monolayer of NHEK, cells were treated with exogenous purified recombinant human PEDF.…”

Section: Resultsmentioning

confidence: 99%

Production and function of pigment epithelium‐derived factor in isolated skin keratinocytes

Chen

DiPietro

2014

Experimental Dermatology

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Pigment epithelium-derived factor (PEDF) is a multifunctional factor with potent anti-angiogenic activity that may play a role in skin homeostasis and wound healing. Analysis of PEDF levels demonstrated that PEDF levels are high in normal skin but quite low in early wounds. As previous studies have suggested that keratinocytes can produce PEDF, we investigated how conditions that mimic those found at sites of injury influence PEDF production by keratinocytes in vitro. Both injury by mechanical disruption (scratch assay) and treatment of human keratinocytes with inflammatory cytokines (IL-1β, IL-6 and TNF-α) inhibited PEDF expression. We next examined how PEDF affects keratinocyte functions that are important in tissue repair. Treatment of keratinocytes with exogenous PEDF enhanced keratinocyte adhesion, therefore impairing migration, while having no effect on cell proliferation. The results suggest that modulation of PEDF levels may play a pivotal role in skin homeostasis and the response of keratinocytes to injury or inflammatory insults.

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Section: Resultsmentioning

confidence: 99%

Production and function of pigment epithelium‐derived factor in isolated skin keratinocytes

Chen

DiPietro

2014

Experimental Dermatology

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“…However, AAPE contained pigment epithelium-derived factor (PEDF), a 50 kDa glyco-protein and a member of the serine protease inhibitor gene family. PEDF inhibits proliferation of HaCaT cells and induces S phase accumulation, and induces a significant decrease of the wound healing of HaCaT cells [42]. The close correlation between scratch wound and cell migration data suggest that PEDF can inhibit migration of HaCaT cells.…”

Section: Resultsmentioning

confidence: 99%

The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes

Moon

Park²,

Lee

et al. 2012

IJMS

107

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Abstract:The beneficial effects of adipose-derived stem cell conditioned medium (ADSC-CM) on skin regeneration have been reported. Although the mechanism of how ADSC-CM promotes skin regeneration is unclear, ADSC-CM contained various growth factors and it is an excellent raw material for skin treatment. ADSC-CM produced in a hypoxia condition of ADSC-in other words, Advanced Adipose-Derived Stem cell Protein Extract (AAPE)-has great merits for skin regeneration. In this study, human primary keratinocytes (HKs), which play fundamental roles in skin tissue, was used to examine how AAPE affects HK. HK proliferation was significantly higher in the experimental group (1.22 μg/mL) than in the control group. DNA gene chip demonstrated that AAPE in keratinocytes (p < 0.05) notably affected expression of 290 identified transcripts, which were associated with cell proliferation, cycle and migration. More keratinocyte wound healing and migration was shown in the experimental group (1.22 μg/mL). AAPE treatment significantly stimulated stress fiber formation, which was linked to the OPEN ACCESS Int. J. Mol. Sci. 2012, 13 1240RhoA-ROCK pathway. We identified 48 protein spots in 2-D gel analysis and selected proteins were divided into 64% collagen components and 30% non-collagen components as shown by the MALDI-TOF analysis. Antibody array results contained growth factor/cytokine such as HGF, FGF-1, G-CSF, GM-CSF, IL-6, VEGF, and TGF-β3 differing from that shown by 2-D analysis. Conclusion: AAPE activates HK proliferation and migration. These results highlight the potential of the topical application of AAPE in the treatment of skin regeneration.

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“…Moreover, plenty of data revealed that metalloproteinases are upregulated by CD9 [25,26]. JNK pathway has been implicated in MMP-9 regulation in human epidermal keratinocytes and HaCaT cells in vitro [27,28] and our previous study revealed that nullification of CD9 upegulates MMP-9 expression in mouse wound healing [14]. However, since CD9 is not only expressed in keratinocytes, but also in other types of cells in skin, it is also unclear whether the observed alteration in JNK or MMP-9 regulation in migrating epidermis in CD9 knockout wounds is directly due to the lack of CD9 in keratinocytes or indirectly due to the influences by other skin cells lacking CD9.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of CD9 in Keratinocyte Contributes to Cell Migration via Upregulation of Matrix Metalloproteinase-9

et al. 2013

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Tetraspanin CD9 has been implicated in various cellular and physiological processes, including cell migration. In our previous study, we found that wound repair is delayed in CD9-null mice, suggesting that CD9 is critical for cutaneous wound healing. However, many cell types, including immune cells, endothelial cells, keratinocytes and fibroblasts undergo marked changes in gene expression and phenotype, leading to cell proliferation, migration and differentiation during wound repair, whether CD9 regulates kerationcytes migration directly remains unclear. In this study, we showed that the expression of CD9 was downregulated in migrating keratinocytes during wound repair in vivo and in vitro. Recombinant adenovirus vector for CD9 silencing or overexpressing was constructed and used to infect HaCaT cells. Using cell scratch wound assay and cell migration assay, we have also demonstrated that downregulation of CD9 promoted keratinocyte migration in vitro, whereas CD9 overexpression inhibited cell migration. Moreover, CD9 inversely regulated the activity and expression of MMP-9 in keratinocytes, which was involved in CD9-regulated keratinocyte migration. Importantly, CD9 silencing-activated JNK signaling was accompanied by the upregulation of MMP-9 activity and expression. Coincidentally, we found that SP600125, a JNK pathway inhibitor, decreased the activity and expression of MMP-9 of CD9-silenced HaCaT cells. Thus, our results suggest that CD9 is downregulated in migrating keratinocytes in vivo and in vitro, and a low level of CD9 promotes keratinocyte migration in vitro, in which the regulation of MMP-9 through the JNK pathway plays an important role.

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Pigment epithelium-derived factor plays an inhibitory role in proliferation and migration of HaCaT cells

Cited by 13 publications

References 23 publications

Production and function of pigment epithelium‐derived factor in isolated skin keratinocytes

Production and function of pigment epithelium‐derived factor in isolated skin keratinocytes

The Effect of Secretory Factors of Adipose-Derived Stem Cells on Human Keratinocytes

Downregulation of CD9 in Keratinocyte Contributes to Cell Migration via Upregulation of Matrix Metalloproteinase-9

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