Significant upregulation of U1 and U4 spliceosomal snRNAs by ATP nanoliposomes explains acceleration of wound healing, due to increased pre-mRNA processing to functional mRNA

Kotwal, Girish J.; Martin, Michael; Chien, Sufan

doi:10.1016/j.nano.2018.03.003

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…Intracellular delivery of ATP 1095 increases the chemical energy which can be used for the various cellular process such as 1096 exocytosis, endocytosis, metabolism, apoptosis, regulate innate immunity, cell differentiation, cell reprogramming, etc. [139]. Direct infusion of exogenous ATP is not possible due to its anionic 1098 charge and hydrophilic nature which forbids delivery through the cellular membrane.…”

Section: Delivery Of Atp5a Protein Via Ev/atp5a Complexes To Ogd-exposed Becsmentioning

confidence: 99%

Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

D’Souza

Burch

Dave

et al. 2021

Preprint

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Extracellular vesicles (EVs) such as exosomes (EXOs) and microvesicles (MVs) are promising carriers for the delivery of biologic drugs such as nucleic acids and proteins. We have demonstrated, for the first time, that EVs derived from hCMEC/D3: a human brain endothelial cell (BEC) line transfer polarized mitochondria to recipient BECs in culture and to neurons in mice acute brain cortical and hippocampal slices. This mitochondrial transfer increased ATP levels by 100 to 200-fold (relative to untreated cells) in the recipient BECs exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. Our previous studies suggested that EXOs, the smaller vesicle subpopulation, derived from a macrophage cell line (RAW264.7) load more exogenous plasmid DNA compared to the larger MVs and the RAW-derived EXOs also demonstrated greater transfection in the recipient BECs compared to EXOs derived from the homotypic hCMEC/D3 BECs. Proteomic analysis of EVs indicated that RAW-EVs are preferentially enriched with proteins that are involved in the trafficking of DNA-containing particles from the cytoplasm towards the nucleus. Intriguingly, although the heterotypic macrophage-derived EVs demonstrated increased transfection in the recipient BECs; the homotypic, BEC-derived EVs demonstrated a greater selectivity to transfer polarized mitochondria and increase endothelial cell survival under ischemic conditions.

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Section: Delivery Of Atp5a Protein Via Ev/atp5a Complexes To Ogd-exposed Becsmentioning

confidence: 99%

Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

D’Souza

Burch

Dave

et al. 2021

Preprint

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show abstract

“…The data sets, supplement each other and confirm and consolidate the overall inference drawn that there is significant upregulation. Our group has recently published advances in RNA analysis by RNA array technique as well as RNA seq technology to obtain an unbiased evaluation of gene expression in rabbit cells in culture treated with ATP nanoliposomes or gamma-thio ATP nanoliposome control (Kotwal et al, 2018). However, many more cells and mediators are known to be involved in the healing process, and upregulation of these cytokines is only part of this rapid tissue growth.…”

Section: The Role Of Mscs and Growth Factorsmentioning

confidence: 99%

Intracellular ATP Delivery Causes Rapid Tissue Regeneration via Upregulation of Cytokines, Chemokines, and Stem Cells

Sarojini

Wan

et al. 2020

Front. Pharmacol.

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We have reported accelerated wound healing induced by intracellular ATP delivery in rabbits, through early massive accumulation, in situ proliferation, and M2 polarization of macrophages. Granulation tissue started to grow within first 24 h of treatment and continued the growth till the wound cavity is completely covered. However, the mechanisms underlying this macrophage response are totally unclear because no one has ever reported this before. In this study, we performed a preliminary exploration of the possible mechanisms by focusing on the roles of cytokines, growth factors, and stem cells in this process. Among the 33 adult rabbits, 18 were used for cytokine measurements and the remaining were used for histological and immunohistochemical studies. Four wounds were created on the ventral side of each ear. Two wounds on one side were treated with ATP-vesicles (10 mM ATP), and the other two were treated with controls (normal saline or Regranex). Dressing changes were made daily and the rabbits were sacrificed at 5 h, 12 h, and 1, 2, 3, 4, 6, 9, 15, and 26 days after wounding. Tissue samples were analyzed for cytokines and growth factors using real-time PCR and immunohistochemical staining. The control wounds showed an immediate increase in proinflammatory cytokines after wound creation but no further increase after this initial spike. The growth factor levels in the control wounds remained unchanged throughout the study. Conversely, the wounds treated with ATP-vesicles showed significantly higher expression of MCP-1 and stem cell markers (CD44, CD106, CD146, and CD34) at day 1, significantly higher IL-1b and TNF-a expression from day 1-4, and significantly higher VEGF-A, VEGF-D, and VEGFR-2 expression from day 4-6 when compared to the controls. The significant upregulation of these factors corresponded to the very early and rapid macrophage accumulation, in situ proliferation, and M2 polarization, resulting in unprecedented rapid granulation tissue generation due to direct macrophage collagen production and neovascularization.

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“…Thus, the accelerated ATP level triggers molecular events, resulting in increased wound healing efficacy. 137 The experimental results clearly showed that ATP plays an important role in the wound healing process and functions as an energy-delivering molecule. Thus, ATP helps in targeting living cells and helps in drug delivery systems.…”

Section: Nanomaterial-based Therapies For Diabetic Foot Ulcersmentioning

confidence: 98%

A review on contemporary nanomaterial-based therapeutics for the treatment of diabetic foot ulcers (DFUs) with special reference to the Indian scenario

et al. 2022

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Significant upregulation of U1 and U4 spliceosomal snRNAs by ATP nanoliposomes explains acceleration of wound healing, due to increased pre-mRNA processing to functional mRNA

Cited by 7 publications

References 23 publications

Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

Microvesicles Transfer Mitochondria and Increase Mitochondrial Function in Brain Endothelial Cells

Intracellular ATP Delivery Causes Rapid Tissue Regeneration via Upregulation of Cytokines, Chemokines, and Stem Cells

A review on contemporary nanomaterial-based therapeutics for the treatment of diabetic foot ulcers (DFUs) with special reference to the Indian scenario

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