Tetrahedral Framework Nucleic Acids Promote Corneal Epithelial Wound Healing in Vitro and in Vivo

Liu, Nanxin; Zhang, Xiaolin; Li, Ni; Zhou, Mi; Zhang, Tianxu; Li, Songhang; Cai, Xiaoxiao; Ji, Ping; Lin, Yunfeng

doi:10.1002/smll.201901907

Cited by 37 publications

(42 citation statements)

References 62 publications

(55 reference statements)

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“…Previous studies have indicated that tFNAs can promote the proliferation of various cell types. 24 – 27 , 29 , 34 , 35 Therefore, in this research, we aimed to determine whether this type of effect also existed in HaCaT and HSF cells. CCK-8 assays were used to examine cell proliferation, while cell-cycle assays were used to analyze changes in the number of cells at each stage.…”

Section: Discussionmentioning

confidence: 99%

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Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

Zhu

Zhang

Gao

et al. 2020

Sig Transduct Target Ther

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While the skin is considered the first line of defense in the human body, there are some vulnerabilities that render it susceptible to certain threats, which is an issue that is recognized by both patients and doctors. Cutaneous wound healing is a series of complex processes that involve many types of cells, such as fibroblasts and keratinocytes. This study showed that tetrahedral framework nucleic acids (tFNAs), a type of self-assembled nucleic-acid material, have the ability to promote keratinocyte(HaCaT cell line) and fibroblast(HSF cell line) proliferation and migration in vitro. In addition, tFNAs increased the secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in HSF cells and reduced the production of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in HaCaT cells by activating the AKT-signaling pathway. During in vivo experiments, tFNA treatments accelerated the healing process in skin wounds and decreased the development of scars, compared with the control treatment that did not use tFNAs. This is the first study to demonstrate that nanophase materials with the biological features of nucleic acids accelerate the healing of cutaneous wounds and reduce scarring, which indicates the potential application of tFNAs in skin tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

“…As shown in previous studies, tFNAs are able to promote cell migration. 27 – 29 , 35 Scratch experiments are widely performed to investigate cell migration in vitro, but there are still factors that can interfere with these outcomes. In this study, to minimize variability, all scratches were made by the same person.…”

Section: Discussionmentioning

confidence: 99%

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

Zhu

Zhang

Gao

et al. 2020

Sig Transduct Target Ther

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“…Total protein was isolated from cells using a total protein extraction kit (Keygen Biotech, Nanjing, China). The protein samples were mixed with loading buffer, boiled for 5 min, separated by SDS-PAGE, and transferred to polyvinylidene fluoride membranes [29,30]. The membranes were blocked with 5% dry skim milk in Tris-buffered saline with 0.05% (v/v) Tween-20 (TBST) for 1 h and then incubated with primary antibodies against JKAMP (NBP2-36446SS) (Novus, Littleton, USA), GAPDH (ab181602), JNK1 (ab110724), β-Catenin (ab32572), RUNX2 (ab92336) and OPN (ab8448) (Abcam, Cambridge, UK), GSK-3β (12456), or p-GSK-3β (5558) (Cell Signaling Technology, Danvers, USA) at 4°C overnight.…”

Section: Western Blot Analysismentioning

confidence: 99%

JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation

et al. 2021

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Background Diabetic osteoporosis (DOP) is a systemic metabolic bone disease caused by diabetes mellitus (DM). Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Our previous study confirmed that ASCs from DOP mice (DOP-ASCs) have a lower osteogenesis potential compared with control ASCs (CON-ASCs). However, the cause of this poor osteogenesis has not been elucidated. Therefore, this study investigated the underlying mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics and explored methods to enhance their osteogenic capacity. Methods The expression level of JNK1-associated membrane protein (JKAMP) and degree of DNA methylation in CON-ASCs and DOP-ASCs were measured by mRNA expression profiling and MeDIP sequencing, respectively. JKAMP small interfering RNA (siRNA) and a Jkamp overexpression plasmid were used to assess the role of JKAMP in osteogenic differentiation of CON-ASCs and DOP-ASCs. Immunofluorescence, qPCR, and western blotting were used to measure changes in expression of Wnt signaling pathway-related genes and osteogenesis-related molecules after osteogenesis induction. Alizarin red and ALP staining was used to confirm the osteogenic potential of stem cells. Bisulfite-specific PCR (BSP) was used to detect JKAMP methylation degree. Results Expression of JKAMP and osteogenesis-related molecules (RUNX2 and OPN) in DOP-ASCs was decreased significantly in comparison with CON-ASCs. JKAMP silencing inhibited the Wnt signaling pathway and reduced the osteogenic ability of CON-ASCs. Overexpression of JKAMP in DOP-ASCs rescued the impaired osteogenic capacity caused by DOP. Moreover, JKAMP in DOP-ASCs contained intragenic DNA hypermethylated regions related to the downregulation of JKAMP expression. Conclusions Intragenic DNA methylation inhibits the osteogenic ability of DOP-ASCs by suppressing expression of JKAMP and the Wnt signaling pathway. This study shows an epigenetic explanation for the reduced osteogenic ability of DOP-ASCs and provides a potential therapeutic target to prevent and treat osteoporosis.

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Section: Western Blot Analysismentioning

confidence: 99%

JKAMP Inhibits the Osteogenic Capacity of Adipose-derived Stem Cells in Diabetic Osteoporosis by Modulating the Wnt Signaling Pathway Through Intragenic DNA Methylation

Peng,

Shi,

Tao

et al. 2020

Preprint

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Background: Diabetic osteoporosis (DOP) is a systemic metabolic bone disease caused by diabetes mellitus (DM). Adipose-derived stem cells (ASCs) play an important role in bone regeneration. Our previous study confirmed that ASCs from DOP mice (DOP-ASCs) have a lower osteogenesis potential compared with control ASCs (CON-ASCs). However, the cause of this poor osteogenesis has not been elucidated. Therefore, this study investigated the underlying mechanism of the decline in the osteogenic potential of DOP-ASCs from the perspective of epigenetics and explored methods to enhance their osteogenic capacity. Methods: The expression level of JNK1-associated membrane protein (JKAMP) and degree of DNA methylation in CON-ASCs and DOP-ASCs were measured by mRNA expression profiling and MeDIP sequencing, respectively. JKAMP small interfering RNA (siRNA) and a Jkamp overexpression plasmid were used to assess the role of JKAMP in osteogenic differentiation of CON-ASCs and DOP-ASCs. Immunofluorescence, qPCR, and western blotting were used to measure changes in expression of Wnt signaling pathway-related genes and osteogenesis-related molecules after osteogenesis induction. Alizarin red and ALP staining was used to confirm the osteogenic potential of stem cells. Bisulfite-specific PCR (BSP) was used to detect JKAMP methylation degree. Results: Expression of JKAMP and osteogenesis-related molecules (RUNX2 and OPN) in DOP-ASCs was decreased significantly in comparison with CON-ASCs. JKAMP silencing inhibited the Wnt signaling pathway and reduced the osteogenic ability of CON-ASCs. Overexpression of JKAMP in DOP-ASCs rescued the impaired osteogenic capacity caused by DOP. Moreover, JKAMP in DOP-ASCs contained intragenic DNA hypermethylated regions related to the downregulation of JKAMP expression. Conclusions: Intragenic DNA methylation inhibits the Wnt signaling pathway by suppressing expression of JKAMP and the osteogenic ability of DOP-ASCs. This study shows an epigenetic explanation for the reduced osteogenic ability of DOP-ASCs, and provides a potential therapeutic target to prevent and treat osteoporosis.

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Tetrahedral Framework Nucleic Acids Promote Corneal Epithelial Wound Healing in Vitro and in Vivo

Cited by 37 publications

References 62 publications

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

Tetrahedral framework nucleic acids promote scarless healing of cutaneous wounds via the AKT-signaling pathway

JKAMP inhibits the osteogenic capacity of adipose-derived stem cells in diabetic osteoporosis by modulating the Wnt signaling pathway through intragenic DNA methylation

JKAMP Inhibits the Osteogenic Capacity of Adipose-derived Stem Cells in Diabetic Osteoporosis by Modulating the Wnt Signaling Pathway Through Intragenic DNA Methylation

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