After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration

Zhu, Amadeus S.; Li, Ang; Ratliff, Tabetha S.; Melsom, M.; Garza, Luis A.

doi:10.1016/j.jid.2017.03.023

Cited by 31 publications

(22 citation statements)

References 21 publications

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“…This is coincident with increased double-stranded RNA (dsRNA) signaling through its receptor DExD/H-Box Helicase 58 (DDX58/RIG-I), which is both sufficient and necessary for KRT9 expression loss. These results support a model in which dsRNA is capable for inducing stem cell behavior and is important early in regeneration (Nelson et al, 2015; Zhu et al, 2017)—but is also a hurdle for maintaining cell identity ex vivo.…”

Section: Introductionsupporting

confidence: 77%

dsRNA Sensing Induces Loss of Cell Identity

Zhou

Wang

Kim³

et al. 2019

Journal of Investigative Dermatology

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How cell and tissue identity persist despite constant cell turnover is an important biologic question with cell therapy implications. Although many mechanisms exist, we investigated the controls for site-specific gene expression in skin, given its diverse structures and functions. For example, the transcriptome of in vivo palmoplantar (i.e., volar) epidermis is globally unique, including Keratin 9 (KRT9). Although volar fibroblasts have the capacity to induce KRT9 in nonvolar keratinocytes, we show here that volar keratinocytes continue to express KRT9 in in vitro solo cultures. Despite this, KRT9 expression is lost with volar keratinocyte passaging, despite stable hypomethylation of its promoter. Coincident with KRT9 loss is a gain of the primitive keratin 7 and a signature of dsRNA sensing, including the double-stranded RNA (dsRNA) receptor DExD/H-Box Helicase 58 (DDX58/RIG-I). Exogenous dsRNA inhibits KRT9 expression in early passage volar keratinocytes or in vivo footpads of wild-type mice. Loss of DDX58 in passaged volar keratinocytes rescues KRT9 and inhibits KRT7 expression. Additionally, DDX58-null mice are resistant to the ability of dsRNA to inhibit KRT9 expression. These results show that the sensing of dsRNA is critical for loss of cell-specific gene expression; our results have important implications for how dsRNA sensing is important outside of immune pathways.

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Section: Introductionsupporting

confidence: 77%

dsRNA Sensing Induces Loss of Cell Identity

Zhou

Wang

Kim³

et al. 2019

Journal of Investigative Dermatology

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“…Because of disturbed antioxidant abilities, UV radiation induces enhanced ROS-mediated modifications in skin cells, particularly in lipid peroxidation, resulting in increased levels of 4-hydroxynonenal (4-HNE) and prostaglandins that may act as signaling molecules [47,87]. Prostaglandins are known pro-inflammatory factors, while 4-HNE forms adducts with a number of different proteins which may affect their activity in various ways [47,67].…”

Section: Introductionmentioning

confidence: 99%

Rutin and ascorbic acid cooperation in antioxidant and antiapoptotic effect on human skin keratinocytes and fibroblasts exposed to UVA and UVB radiation

et al. 2019

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The combination of ascorbic acid and rutin is frequently used in oral preparations. However, despite numerous protective effects of each component individually, their combined effect on ultraviolet (UV)-irradiated skin cells has never been evaluated. The aim of this study was to evaluate the combined effect of ascorbic acid and rutin on human keratinocytes and fibroblasts exposed to UVA and UVB radiation. Skin keratinocytes and fibroblasts exposed to UVA and UVB radiation were treated with ascorbic acid or/and rutin. The total antioxidant properties of both components, as well as their effect on cellular pro-and antioxidant status, lipid and protein oxidation, transmembrane transport, and pro-inflammatory and pro/ antiapoptotic protein expression were measured. The combination of ascorbic acid and rutin had higher antioxidant properties compared to the activity of the single compound alone, and showed a stronger effect against UV-induced reactive oxygen species generation. The ascorbic acid and rutin combination also showed increased antioxidant enzyme activity (catalase, superoxide dismutase, thioredoxin reductase), which was impaired following UV irradiation. Moreover, ascorbic acid additional stimulated UV-induced bilitranslocase activity responsible for rutin transport, and therefore favored rutin effect on Nrf2 pathway, simultaneously differentiating the reaction of keratinocytes and fibroblasts. In keratinocytes, Nrf2 is strongly activated, while in fibroblasts decreased Nrf2 activity was observed. Used mixture, also significantly silenced UV-induced expression of pro-inflammatory factor NFκB and pro-apoptotic proteins such as caspases 3, 8, and 9. These results showed that ascorbic acid and rutin are complementary in their antioxidant actions, transport and signaling functions. Their combined antioxidant, antiinflammatory and antiapoptotic actions suggest rutin and ascorbic acid are a potentially cytoprotective team against UV-induced skin damage.

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“…Intriguingly, cells stemness was induced by inflammatory pathways, which intersected with programmed cell death pathways to some extent. It was mentioned above that de-differentiation of mature keratinocytes, and their acquisition of stem features may be associated with the influence of such an inflammatory agent as dsRNA, as well as upregulation of cytokines IL-17 and IL-22, which occurs during wound healing (Sasaki et al, 2011;Zhu et al, 2017). At the same time, the effect of dsRNA on TLR3 is a proven trigger of apoptosis and necroptosis (Seya et al, 2012) and upregulation of IL-17 and IL-22 in the psoriasis model is associated with a decrease in the expression of a RIPK-1, traditionally considered as a necroptosis component (Saito et al, 2018).…”

Section: Episc Plasticity During Wound Healing Under the Influence Ofmentioning

confidence: 99%

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

Morgun

Vorotelyak

2020

Front. Cell Dev. Biol.

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After Skin Wounding, Noncoding dsRNA Coordinates Prostaglandins and Wnts to Promote Regeneration

Cited by 31 publications

References 21 publications

dsRNA Sensing Induces Loss of Cell Identity

dsRNA Sensing Induces Loss of Cell Identity

Rutin and ascorbic acid cooperation in antioxidant and antiapoptotic effect on human skin keratinocytes and fibroblasts exposed to UVA and UVB radiation

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

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