Barrier Function of the Repaired Skin Is Disrupted Following Arrest of Dicer in Keratinocytes

Ghatak, Subhadip; Chan, Yuk Cheung; Khanna, Savita; Banerjee, Jaideep; Weist, Jessica; Roy, Sashwati; Sen, Chandan K.

doi:10.1038/mt.2015.65

Cited by 45 publications

(41 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Waf1/Cip1 might be a potential drug target to improve barrier function of the skin during Dicer loss (44). Identification of decreased Dicer levels during impaired wound healing in diabetes in our study, therefore, offers a valuable tool to be addressed such that the delay in the wound-healing process during diabetes might be targeted.…”

Section: Resultsmentioning

confidence: 81%

“…These mice depict a marginal increase in apoptosis in the skin and start losing weight 1-2 d after birth (42,43). Oxidative insult can decrease Dicer levels as in observed in several pathological states (44,45). Although, in the context of endothelial cells, conditional Dicer inactivation reduces vascular endothelial growth Figure 6.…”

Section: Interaction Among the Mirna Predicted Targets And Altered Womentioning

confidence: 91%

See 1 more Smart Citation

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Bhattacharya

Aggarwal

Singh

et al. 2015

Mol Med

View full text Add to dashboard Cite

Delayed wound healing is a major complication associated with diabetes and is a result of a complex interplay among diverse deregulated cellular parameters. Although several genes and pathways have been identified to be mediating impaired wound closure, the role of microRNAs (miRNAs) in these events is not very well understood. Here, we identify an altered miRNA signature in the prolonged inflammatory phase in a wound during diabetes, with increased infiltration of inflammatory cells in the basal layer of the epidermis. Nineteen miRNAs were downregulated in diabetic rat wounds (as compared with normal rat wound, d 7 postwounding) together with inhibited levels of the central miRNA biosynthesis enzyme, Dicer, suggesting that in wounds of diabetic rats, the decreased levels of Dicer are presumably responsible for miRNA downregulation. Compared with unwounded skin, Dicer levels were significantly upregulated 12 d postwounding in normal rats, and this result was notably absent in diabetic rats that showed impaired wound closure. In a wound-healing specific quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) array, 10 genes were significantly altered in the diabetic rat wound and included growth factors and collagens. Network analyses demonstrated significant interactions and correlations between the miRNA predicted targets (regulators) and the 10 wound-healing specific genes, suggesting altered miRNAs might fine-tune the levels of these genes that determine wound closure. Dicer inhibition prevented HaCaT cell migration and affected wound closure. Altered levels of Dicer and miRNAs are critical during delayed wound closure and offer promising targets to address the issue of impaired wound healing.

show abstract

Section: Resultsmentioning

confidence: 81%

Section: Interaction Among the Mirna Predicted Targets And Altered Womentioning

confidence: 91%

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Bhattacharya

Aggarwal

Singh

et al. 2015

Mol Med

View full text Add to dashboard Cite

show abstract

“…10 Measurement sites included areas of low stress (site 1 TT, sites 2 and 4 TF) and high stress (sites 2, 3, 4 TT, sites 1 and 3 TF). AL measurement sites were matched to TT sites.…”

Section: Skin Health Measurementsmentioning

confidence: 99%

Standardized Approach to Quantitatively Measure Residual Limb Skin Health in Individuals with Lower Limb Amputation

Rink

Wernke

Powell

et al. 2017

Advances in Wound Care

View full text Add to dashboard Cite

Objective: (1) Develop a standardized approach to quantitatively measure residual limb skin health. (2) Report reference residual limb skin health values in people with transtibial and transfemoral amputation. Approach: Residual limb health outcomes in individuals with transtibial (n = 5) and transfemoral (n = 5) amputation were compared to able-limb controls (n = 4) using noninvasive imaging (hyperspectral imaging and laser speckle flowmetry) and probe-based approaches (laser doppler flowmetry, transcutaneous oxygen, transepidermal water loss, surface electrical capacitance). Results: A standardized methodology that employs noninvasive imaging and probebased approaches to measure residual limb skin health are described. Compared to able-limb controls, individuals with transtibial and transfemoral amputation have significantly lower transcutaneous oxygen tension, higher transepidermal water loss, and higher surface electrical capacitance in the residual limb. Innovation: Residual limb health as a critical component of prosthesis rehabilitation for individuals with lower limb amputation is understudied in part due to a lack of clinical measures. Here, we present a standardized approach to measure residual limb health in people with transtibial and transfemoral amputation. Conclusion: Technology advances in noninvasive imaging and probe-based measures are leveraged to develop a standardized approach to quantitatively measure residual limb health in individuals with lower limb loss. Compared to able-limb controls, resting residual limb physiology in people that have had transfemoral or transtibial amputation is characterized by lower transcutaneous oxygen tension and poorer skin barrier function.

show abstract

“…LNA based anti-miR-210 and negative control were purchased from Exiqon. miRNA isolation, Western blot, immunohistochemistry was performed as describe previously 7 . For further details see supplementary materials.…”

Section: Methodsmentioning

confidence: 99%

AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against ischemic memory improving cutaneous wound healing

Ghatak

Chan

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

Self Cite

View full text Add to dashboard Cite

Peripheral vasculopathies cause severe wound hypoxia inducing the hypoxamiR miR-210. High level of miR-210, persisting in wound-edge tissue as ischemic memory, suppresses oxidative metabolism and inhibits cell proliferation necessary for healing. In wound-edge tissue of chronic wound patients, elevated miR-210 was tightly associated with inhibition of epidermal cell proliferation as evident by lowered Ki67 immunoreactivity. To inhibit miR-210 in murine ischemic wound-edge tissue, we report the formulation of antihypoxamiR functionalized gramicidin lipid nanoparticles (AFGLN). A single intradermal delivery of AFGLN encapsulating LNA-conjugated anti-hypoximiR-210 (AFGLNmiR-210) lowered miR-210 level in the ischemic wound-edge tissue. In repTOP™mitoIRE mice, AFGLNmiR-210 rescued keratinocyte proliferation as visualized by in vivo imaging system (IVIS). 31P NMR studies showed elevated ATP content at the ischemic wound-edge tissue following AFGLNmiR-210 treatment indicating recovering bioenergetics necessary for healing. Consistently, AFGLNmiR-210 improved ischemic wound closure. The nanoparticle based approach reported herein is effective for miR-directed wound therapeutics warranting further translational development.

show abstract

Barrier Function of the Repaired Skin Is Disrupted Following Arrest of Dicer in Keratinocytes

Cited by 45 publications

References 61 publications

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Downregulation of miRNAs during Delayed Wound Healing in Diabetes: Role of Dicer

Standardized Approach to Quantitatively Measure Residual Limb Skin Health in Individuals with Lower Limb Amputation

AntihypoxamiR functionalized gramicidin lipid nanoparticles rescue against ischemic memory improving cutaneous wound healing

Contact Info

Product

Resources

About