Kruppel-like factor 4 regulates keratinocyte senescence

Panatta, Emanuele; Lena, Anna Maria; Mancini, Mara; Affinati, Michela; Smirnov, Artem; Annicchiarico-Petruzzelli, Margherita; Piro, María Cristina; Campione, Elena; Bianchi, Luca; Mazzanti, Cinzia; Melino, Gerry; Candi, Eleonora

doi:10.1016/j.bbrc.2018.03.172

Cited by 12 publications

(14 citation statements)

References 40 publications

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“…As integrin function as a cell surface receptor that provides several survival and proliferation signals, and such signals such as AKT [64] and Wnt/β-catenin [65] activate stemness of cells, it is possible that collagen in our study may, at least in part, activate stemness through integrin- β-catenin-dependent mechanism. From the results, abalone collagen potentiates stemness properties of keratinocytes, which are important for epidermal homeostasis and skin barrier function [66,67]. Additionally, collagen from other sources, such as sponge, has been found to stimulate and increase cell growth, exhibit antioxidant activity, and protect cells from UV-induced death [37].…”

Section: Resultsmentioning

confidence: 99%

Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes

Thaweekitphathanaphakdee

Chanvorachote

Prateepchinda

et al. 2019

Marine Drugs

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Stem cell activities in human tissues are critical for tissue integrity and function. Maintaining keratinocyte stem cells (KSCs) stemness helps sustain healthy skin by supporting keratinocyte renewal, involving the formation of epidermal barriers. In this study, abalone collagen (AC) extracts with molecular weights of 3 kDa (AC 1) and 300 kDa (AC 2) were compared to the epidermal growth factor (EGF) for their effects on cell proliferation, cell migration (wound healing), spheroid formation, and the expression level of stem cell markers on human keratinocytes (HaCaT cells). Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell proliferation was quantified by ATP and DNA content analysis and Sulforhodamine B (SRB) assays. Cell migration assay was determined using the scratch wound healing test. Spheroid formation was evaluated and the expression level of stem cell markers was investigated by western blot analysis. The results showed that AC 1 at the concentration of 100 µg/mL could stimulate HaCaT cell proliferation, migration, spheroid formation, and the expression level of stem cell markers (keratin 19, β-catenin, ALDH1A1) compared to the control. In conclusion, a smaller molecular weight of abalone collagen extract exhibits a better effect on keratinocytes proliferation, migration, and stemness, which could be a potential active ingredient in cosmeceutical products.

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Section: Resultsmentioning

confidence: 99%

Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes

Thaweekitphathanaphakdee

Chanvorachote

Prateepchinda

et al. 2019

Marine Drugs

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“…Notably, the expression of KLF4 decreases during chronological epidermal aging and keratinocyte replicative senescence. Specifically, KLF4 silencing is sufficient to induce a senescent phenotype in primary keratinocytes [155]. Furthermore, Brg1 drives SAHF formation during senescence via its chromatin remodeling activity and/or by up-regulating p16 INK4a expression.…”

Section: Epigenetic Changes In Skin Agingmentioning

confidence: 99%

Epigenetic Regulation of Skin Cells in Natural Aging and Premature Aging Diseases

Orioli

Dellambra

2018

Cells

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Skin undergoes continuous renewal throughout an individual’s lifetime relying on stem cell functionality. However, a decline of the skin regenerative potential occurs with age. The accumulation of senescent cells over time probably reduces tissue regeneration and contributes to skin aging. Keratinocytes and dermal fibroblasts undergo senescence in response to several intrinsic or extrinsic stresses, including telomere shortening, overproduction of reactive oxygen species, diet, and sunlight exposure. Epigenetic mechanisms directly regulate skin homeostasis and regeneration, but they also mark cell senescence and the natural and pathological aging processes. Progeroid syndromes represent a group of clinical and genetically heterogeneous pathologies characterized by the accelerated aging of various tissues and organs, including skin. Skin cells from progeroid patients display molecular hallmarks that mimic those associated with naturally occurring aging. Thus, investigations on progeroid syndromes strongly contribute to disclose the causal mechanisms that underlie the aging process. In the present review, we discuss the role of epigenetic pathways in skin cell regulation during physiologic and premature aging.

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“…Upregulation of JNK by galectin-7 [19] Increased keratinocyte differentiation with involucrin expression by oleic acid [20] p63, Skp2 and Msi2 Promotion of cell cycle exit in mouse skin [21] miR-574 ↑ p63 As direct targets of iASPP [22] miR-720 ↑ miR-24 ↑ PAK4 Control of actin cable formation [23] miR-23b-3p ↑ TGIF1 Interference in TGF-β/SMAD signaling [24] miR-378b ↑ NKX3.1 [25] miR-30a ↑ LOX, IDH1, AVEN Barrier function defects in aged epidermis [26] miR-184 ↑ Upregulation of cyclin E and p21 cyclin-dependent kinase inhibitor in a SOCE-dependent manner [27] miR-181a ↑ cell differentiation under high calcium or UVA exposure [28,29] miR [33] miRNAs targeted by p63 miR-34a ↑ SIRT6 miR-34a and miR-34c as direct targets of p63 [34,35] miR-34a ↑ KLK4 Induction of a senescent phenotype in keratinocytes [36] ↑: upregulation (increase), ↓: downregulation (decrease).…”

Section: Snai2 and ∆Np63mentioning

confidence: 99%

“…Expression of epidermal differentiation complex protein is regulated by a pool of transcription factors, including Kruppel-like factor 4 (KLF4) [44]. Upregulation of miR-34a, which has also been associated with physiological skin aging, inhibits the expression of KLF4 by inducing a senescent phenotype in primary keratinocytes [36].…”

Section: P63mentioning

confidence: 99%

The Role of MicroRNAs in Epidermal Barrier

Lee

2020

IJMS

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MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications.

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Kruppel-like factor 4 regulates keratinocyte senescence

Cited by 12 publications

References 40 publications

Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes

Abalone Collagen Extracts Potentiate Stem Cell Properties of Human Epidermal Keratinocytes

Epigenetic Regulation of Skin Cells in Natural Aging and Premature Aging Diseases

The Role of MicroRNAs in Epidermal Barrier

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