Whey Derivatives and Galactooligosaccharides Stimulate the Wound Healing and the Function of Human Keratinocytes through the NF-kB and FOXO-1 Signaling Pathways

Abstract

Skin repair requires the activation of keratinocytes and is mediated by controlled inflammation and cell migration and proliferation, ending with the regeneration of well-differentiated cell layers. Whey derivatives contain galactooligosaccharides (GOS), which have potential beneficial effects on wound healing due to their activity as toll-like receptor ligands, although their direct nonprebiotic effects in the skin have not yet been described. In this study, we investigated the effects of different whey-derived products and purified GOS on a human keratinocyte cell line. We found that the inflammatory cytokine interleukin-8 (IL-8) was upregulated by nuclear factor kappa B (NF-kB) signaling triggered by whey derivatives and GOS and that wound healing was accelerated by promoting cell migration and the loss of E-cadherin in the absence of epithelial–mesenchymal transition. Interestingly, the treatments enhanced the mitochondrial function in association with the translocation of the Forkhead Box O1 (FOXO-1) transcription factor. Finally, we detected the increased expression of the differentiation markers induced by GOS and whey derivatives. All together, our results show that GOS-containing products can promote wound closure and skin health by direct activity on keratinocyte functions. Among the preparations tested, the fermented compound produced by autochthonous microorganisms was the most active in modulating keratinocyte activity, supporting the biological value of whey derivatives for health.

Artificial and Natural Sweeteners Biased T1R2/T1R3 Taste Receptors Transactivate Glycosylated Receptors on Cancer Cells to Induce Epithelial–Mesenchymal Transition of Metastatic Phenotype

“…Lactose is known to regulate insulin secretion [ 35 ]. Whey protein consumption, which contains lactose and galactooligosaccharide, is linked to NF-κB signaling [ 36 ]. A recent study found that 2′-fucosyllactose and 6′-sialyllactose, derivatives of lactose, inhibited TLR-4 activation, although lactose itself did not [ 37 ].…”

Mannose‐Decorated Co‐Polymer Facilitates Controlled Release of Butyrate to Accelerate Chronic Wound Healing

“…[77] Butyrate has been shown to induce keratinocyte differentiation and improved wound closure in vitro. [78,79] Furthermore, it has recently been shown that butyrate promotes and accelerates the differentiation of epidermal keratinocytes by directly altering their metabolism, enhancing skin barrier function. [80] pMan-But treatment may induce keratinocyte differentiation and migration through a butyrate-mediated metabolic shift, ultimately improving wound closure.…”

Vitamin D and Sulforaphane Decrease Inflammatory Oxidative Stress and Restore the Markers of Epithelial Integrity in an In Vitro Model of Age-Related Macular Degeneration

“…The RT-PCR primers were designed with NCBI/Primer-BLAST and synthesized by Merck (Milan, Italy). Quantitative PCR was carried out in a final volume of 25 µL using the IQ™ SYBR Green Supermix (Bio-Rad Laboratories AG, Cressier FR, Switzerland) with specific primers for the quantitation of the following human genes: cytochrome c oxidase subunit 2 (COXII; fwd 5 ′ -TCTGGTCAGCCCAACTCTCT-3 ′ , rev 5 ′ -CCTGTGATCCACCAGAAGGT-3 ′ , mitochondrial ATP synthase F0 subunit 6 (MT-ATP6; fwd 5 ′ -CCAATAGCCCTGGCCGTAC-3 ′ , rev 5 ′ -CGCTTCCAATTAGGTGCATGA-3 ′ ), mitochondrial ATP synthase F1 β subunit (ATP5B, fwd 5 ′ -GTGGGCTATCAGCCTACCCT-3 ′ , rev 5 ′ -CAAGTCATCAGCAGGCACAT-3 ′ [74], interleukin-6 (IL-6, fwd 5 ′ -GGTACATCCTCGACGGCATCT-3 ′ , rev 5 ′ -GTGCCTCTTTG CTGCTTTCAC-3 ′ ) [73], interleukin-8 (IL-8, fwd 5 ′ -GGAGAAGTTTTTGAAGAGGGCTGA-3 ′ , rev 5 ′ -TGCTTGAAGTTTCACTGGCATCTT-3 ′ ), the junction adhesion and stent protein zonula occluden-1 (ZO-1, fwd 5 ′ -AAAGAGAAAGGTGAAACACTGC-3 ′ , rev 5 ′ -TTTTAGA GCAAAAGACCAACCG-3 ′ ) [18], E-cadherin (E-cadherin, fwd 5-′ TACGCCTGGGACTCCA CCTA-3 ′ , rev 5 ′ -CCAGAAACGGAGGCCTGAT-3 ′ ) and closure protein-4 (claudin 4, CLDN4; 5' CCACAACATCATCCAAGACTTC-3 ′ , rev 5 ′ -CAGAATACTTGGCGGAGTAAGG-3 ′ [75]. PCR amplification was conducted with 1 cycle of denaturation at 95 • C for 2 min, 45 cycles of amplification including denaturation at 95 • C for 15 s, and annealing/extension at 60 • C for 30 s. Data were analyzed using the 2−DDCT, and the housekeeping gene beta-2 microglobulin (β2M, fwd 5 ′ -AGCAAGGACTGGTCTTTCTATCTC-3 ′ , rev 5 ′ -ATGTCTCGATCCCACT TAACTA-3 ′ ) was used as the reference gene to normalize the cDNA in different samples.…”