scholarly journals The role of nitric oxide during embryonic wound healing

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Pavel Abaffy ◽  
Silvie Tomankova ◽  
Ravindra Naraine ◽  
Mikael Kubista ◽  
Radek Sindelka
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Late Phase ◽  
Health Sector ◽  
The Elderly ◽  
Tissue Remodelling ◽  
Expression Of Genes ◽  
Complex Process ◽  
Medical Burden

Abstract Background The study of the mechanisms controlling wound healing is an attractive area within the field of biology, with it having a potentially significant impact on the health sector given the current medical burden associated with healing in the elderly population. Healing is a complex process and includes many steps that are regulated by coding and noncoding RNAs, proteins and other molecules. Nitric oxide (NO) is one of these small molecule regulators and its function has already been associated with inflammation and angiogenesis during adult healing. Results Our results showed that NO is also an essential component during embryonic scarless healing and acts via a previously unknown mechanism. NO is mainly produced during the early phase of healing and it is crucial for the expression of genes associated with healing. However, we also observed a late phase of healing, which occurs for several hours after wound closure and takes place under the epidermis and includes tissue remodelling that is dependent on NO. We also found that the NO is associated with multiple cellular metabolic pathways, in particularly the glucose metabolism pathway. This is particular noteworthy as the use of NO donors have already been found to be beneficial for the treatment of chronic healing defects (including those associated with diabetes) and it is possible that its mechanism of action follows those observed during embryonic wound healing. Conclusions Our study describes a new role of NO during healing, which may potentially translate to improved therapeutic treatments, especially for individual suffering with problematic healing.

Acceleration of Palatal Wound Healing in Smad3-deficient Mice

2009 ◽  
Vol 88 (8) ◽  
pp. 757-761 ◽  
Author(s):  
K. Jinno ◽  
T. Takahashi ◽  
K. Tsuchida ◽  
E. Tanaka ◽  
K. Moriyama
Keyword(s):  
Wound Healing ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Monocyte Chemoattractant Protein 1 ◽  
Inflammatory Protein ◽  
Complex Process ◽  
Dermal Cells ◽  
Macrophage Inflammatory Protein ◽  
Tgf Β1

Wound healing is a well-orchestrated complex process leading to the repair of injured tissues. It is suggested that transforming growth factor (TGF)-β/Smad3 signaling is involved in wound healing. The purpose of this study was to investigate the role of TGF-β/Smad3 signaling in palatal wound healing in Smad3-deficient (Smad3−/−) mice. Histological examination showed that wound closure was accelerated by the proliferation of epithelium and dermal cells in Smad3−/− mice compared with wild-type (WT) mice. Macrophage/monocyte infiltration at wounded regions in Smad3−/− mice was decreased in parallel with the diminished production of TGF-β1, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α compared with WT mice. Fibrocytes, expressing hematopoietic surface marker and fibroblast products, were recruited and produced α-smooth-muscle actin in WT mice, but were not observed in Smad3−/− mice. These results suggest that TGF-β/Smad3 signaling may play an important role in the regulation of palatal wound healing.

Nitric Oxide is a Mediator of the Late-Phase Response in an Animal Model of Nasal Allergy

2000 ◽  
Vol 122 (5) ◽  
pp. 706-711 ◽  
Author(s):  
William F. Durland ◽  
Andrew P. Lane ◽  
Kimberly W. Durland ◽  
Timothy L. Smith ◽  
Kenneth L. Johnson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Inflammatory Cell ◽  
Late Phase ◽  
Phase Response ◽  
Brown Norway ◽  
Nasal Allergy ◽  
Synthase Inhibitor ◽  
Histamine Challenge

The presence of nitric oxide (NO) in the nose is well documented; however, the role of this molecule in nasal physiology is still poorly understood. Our laboratory has previously demonstrated that NO is a mediator of the immediate secretory response to an intranasal histamine challenge in a rat model of nasal allergy. Histamine challenge, however, does not elicit a late-phase response (LPR). To study the role of NO in the LPR, we developed a model of nasal allergy in which brown Norway rats are actively sensitized to the allergen ovalbumin and later challenged intranasally with either phosphate-buffered saline solution (vehicle), ovalbumin in vehicle, or ovalbumin and the NO synthase inhibitor N-nitro-L-arginine methyl ester. In each experiment, nasal lavage samples were collected 30, 120, 240, and 360 minutes after challenge. Lavage samples were analyzed for albumin content by ELISA, inflammatory cell concentration with a hemocytometer, and evidence of inflammation by light microscopy. Blocking NO synthesis with N-nitro-L-arginine methyl ester significantly inhibited both albumin exudation and inflammatory cell influx into the nasal cavity during the LPR. These data suggest that NO plays a role in the LPR of nasal allergy.

scholarly journals Hydrogel cross-linking–programmed release of nitric oxide regulates source-dependent angiogenic behaviors of human mesenchymal stem cell

2020 ◽  
Vol 6 (9) ◽  
pp. eaay5413 ◽  
Author(s):  
Mi-Lan Kang ◽  
Hye-Seon Kim ◽  
Jin You ◽  
Young Sik Choi ◽  
Byeong-Ju Kwon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bone Marrow ◽  
Wound Healing ◽  
Human Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cell ◽  
Tube Formation ◽  
Cross Linking ◽  
No Production ◽  
Gelatin Hydrogel

Angiogenesis is stimulated by nitric oxide (NO) production in endothelial cells (ECs). Although proangiogenic actions of human mesenchymal stem cells (hMSCs) have been extensively studied, the mechanistic role of NO in this action remains obscure. Here, we used a gelatin hydrogel that releases NO upon crosslinking by a transglutaminase reaction (“NO gel”). Then, the source-specific behaviors of bone marrow versus adipose tissue-derived hMSCs (BMSCs versus ADSCs) were monitored in the NO gels. NO inhibition resulted in significant decreases in their angiogenic activities. The NO gel induced pericyte-like characteristics in BMSCs in contrast to EC differentiation in ADSCs, as evidenced by tube stabilization versus tube formation, 3D colocalization versus 2D coformation with EC tube networks, pericyte-like wound healing versus EC-like vasculogenesis in gel plugs, and pericyte versus EC marker production. These results provide previously unidentified insights into the effects of NO in regulating hMSC source-specific angiogenic mechanisms and their therapeutic applications.

Understanding the Potential Role and Delivery Approaches of Nitric Oxide in the Chronic Wound Healing Management

2020 ◽  
Vol 26 ◽  
Author(s):  
Mimansa Kandhwal ◽  
Tapan Behl ◽  
Arun Kumar ◽  
Sandeep Arora
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Chronic Wound ◽  
Lower Limbs ◽  
Diabetic Patients ◽  
Pharmacological Mechanism ◽  
Novel Treatments ◽  
Beneficial Effects ◽  
Chronic Ulcers

: Nitric oxide (NO) is a promising pharmaceutical component that has vasodilator, antibacterial and wound healing activity. Chronic ulcers are non-healing disorders that are generally associated with distortion of lower limbs. Among the severe consequence’s derivative of these diseases, are the problems of chronic wound progression. NO which is categorized as smallest gaseous neurotransmitter has beneficial effects in different phases of chronic inflammation. Defensive mechanism of NO is found useful in several severe conditions such as gestational healing, gastrointestinal healing and diabetic healing. The current review presents up to date collection of literature about role of NO in chronic ulcers due to the prevalence of diabetes, DPN, and diabetic foot ulcers, and because of the lack of available effective treatments to directly address the pathology contributing to these conditions, novel treatments are being sought. This review also collects the information about deficiency of NO synthase in diabetic patients leads to a lack of vascularization of the peripheral nerves, which causes diabetic neuropathy; and this could be treated with vasodilators such as nitric oxide. Apart from pharmacological mechanism of NO, the article also reviewed and analyzed to elucidate the potential of a transdermal delivery of NO for the treatment of chronic ulcers.

TACROLIMUS (TA) IMPAIRS WOUND HEALING: ROLE OF NITRIC OXIDE (NO) SYNTHESIS

Shock ◽  
1997 ◽  
Vol 7 (Supplement) ◽  
pp. 125-126
Author(s):  
M Schäffer ◽  
N Fuchs ◽  
G Köveker ◽  
H D Becker
Keyword(s):  
Nitric Oxide ◽  
Wound Healing

scholarly journals Asthma In The Elderly: The Role Of Exhaled Nitric Oxide Measurements

2012 ◽  
Vol 129 (2) ◽  
pp. AB8 ◽  
Author(s):  
M. Columbo ◽  
B. Wong ◽  
R.A. Panettieri ◽  
A.S. Rohr
Keyword(s):  
Nitric Oxide ◽  
The Elderly ◽  
Exhaled Nitric Oxide

scholarly journals Passive leg movement and nitric oxide-mediated vascular function: the impact of age

2015 ◽  
Vol 308 (6) ◽  
pp. H672-H679 ◽  
Author(s):  
Joel D. Trinity ◽  
H. Jonathan Groot ◽  
Gwenael Layec ◽  
Matthew J. Rossman ◽  
Stephen J. Ives ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Function ◽  
Area Under The Curve ◽  
The Elderly ◽  
Novel Approach ◽  
Leg Movement ◽  
The Impact ◽  
Male Subjects ◽  
Peak Increase

In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of NG-monomethyl-l-arginine (l-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106; l-NMMA: 431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98; l-NMMA: 251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: −31 ± 18 ml) than the young (LBF: −129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.

scholarly journals The Nitrate-Nitrite-Nitric Oxide Pathway on Healthy Ageing: A Review of Pre-clinical and Clinical Data on the Impact of Dietary Nitrate in the Elderly

2021 ◽  
Vol 2 ◽  
Author(s):  
Bárbara S. Rocha
Keyword(s):  
Nitric Oxide ◽  
Free Radicals ◽  
Clinical Data ◽  
The Elderly ◽  
Healthy Ageing ◽  
Leafy Vegetables ◽  
Metabolic Effects ◽  
Radical Theory ◽  
The Impact

We are living longer. Are we living healthier? As we age, cellular and molecular damage reshape our physiological responses towards environmental and endogenous stimuli. The free radical theory of ageing has been proposed long before ageing has been considered a “scientific discipline” and, since then, has been discussed and upgraded as a major contributor to aberrant ageing. Assuming that ageing results merely from the accumulation of oxidative modifications of biomolecules is not only a simplistic and reductive view of such a complex and dynamic process, but also free radicals and related oxidants are now considered pivotal signalling molecules. The fine modulation of critical signalling pathways by redox compounds demands a novel approach to tackle the role of free radicals in ageing. Nitric oxide (⋅NO) is a paradigmatic example given its biological functions in cardiovascular, neurologic and immune systems. In addition to the canonical ⋅NO synthesis by a family of enzymes, nitrate from green leafy vegetables, is reduced to nitrite in the oral cavity which is further reduced to ⋅NO in the stomach. Boosting this nitrate-nitrite-NO pathway has been shown to improve gastrointestinal, cardiovascular, metabolic and cognitive performance both in humans and in animal models of disease. In the elderly, nitrate-derived ⋅NO has been shown improve several physiological functions that typically decline during ageing. In this paper, the role of nitrate and derived nitrogen oxides will be discussed while reviewing pre-clinical and clinical data on the cardiovascular, neuronal, musculoskeletal and metabolic effects of nitrate during healthy ageing.

Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse

1994 ◽  
Vol 107 (5) ◽  
pp. 1159-1167 ◽  
Author(s):  
J. Hopkinson-Woolley ◽  
D. Hughes ◽  
S. Gordon ◽  
P. Martin
Keyword(s):  
Wound Healing ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Limb Development ◽  
Close Association ◽  
Active Role ◽  
Tissue Remodelling ◽  
Fibroblastic Cells ◽  
Made In

Macrophages play a pivotal role in the adult inflammatory response to wounding. They are directly responsible for cellular debridement and, by providing a source of growth factors and cytokines, they recruit other inflammatory and fibroblastic cells and influence cell proliferation and tissue remodelling. In this paper we investigate the role of macrophages in clearing areas of programmed cell death in the developing embryo and also their role in embryonic and foetal wound healing. Immunocytochemistry using the monocyte/macrophage-specific monoclonal antibody, F4/80, reveals a close association between areas of programmed cell death in the remodelling interdigital regions of the mouse footplate and of F4/80-positive cells, suggesting that monocyte-derived macrophages, and not locally recruited fibroblastic cells, as previously believed, are responsible for phagocytosing and clearing areas of interdigital apoptosis. Our studies of wound healing reveal that macrophages are not recruited to, and therefore cannot be playing an active role in the healing of, excisional wounds made in the mouse embryo at any stage up until E14.5. Beyond this transition stage we see a significant recruitment of macrophages within 12 hours of wounding. We find that macrophages can be attracted to wounds in earlier embryos if the wound results in significant cell death such as after burning.

Nitric oxide donors retard wound healing in cultured rabbit gastric epithelial cell monolayers

2001 ◽  
Vol 281 (5) ◽  
pp. G1151-G1157 ◽  
Author(s):  
Tuula Kiviluoto ◽  
Sumio Watanabe ◽  
Miyoko Hirose ◽  
Nobuhiro Sato ◽  
Harri Mustonen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Wound Healing ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Cell Cultures ◽  
Cell Apoptosis ◽  
Gastric Epithelial Cell ◽  
Dependent Manner ◽  
No Donor

Effects of nitric oxide (NO) on gastric wound healing were investigated in primary rabbit gastric epithelial cell cultures. We analyzed the speed of cell migration, proliferation, and apoptosis after creating a round wound on the cell cultures. The monolayers were incubated with or without the NO donor sodium nitroprusside, oxatriazolimine 1,2,3,4-oxatriazolium, 5amino-3-(3,4-dichlorophenylchloride), or the peroxynitrite generator 3-morpholinosydnomine- N-ethylcarbamide. The possible role of cGMP as a second messenger of NO was investigated with 8-bromo-cGMP. The role of O[Formula: see text]· was evaluated using diethyldithiocarbamate and pyrogallol. The effects of superoxide dismutase and allopurinol were also investigated. NO inhibited the speed of cell migration and proliferation and induced cell apoptosis in a dose- and time-dependent manner. The effects were augmented with O[Formula: see text]· generators and ameliorated by O[Formula: see text]· scavengers, whereas cGMP had no significant effect on wound healing. NO donors retard gastric wound healing by inhibiting migration and proliferation and inducing cell apoptosis. These effects do not seem to be mediated via cGMP, but O[Formula: see text]· or peroxynitrites may be involved.

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