Mitogen‐activated kinase pathway activation in epidermal lamellae in the acute stages of carbohydrate overload laminitis models and the effect of regional deep hypothermia on signalling pathways

Gardner, Alison; Kelly, Cheryl; Eps, A. W. van; Burns, T.A.; Watts, M.; Belknap, James K.

doi:10.1111/evj.12488

Cited by 9 publications

(9 citation statements)

References 33 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore enzyme activation may be assessed in cell lysates by Western blotting using antibodies specific to the phosphorylated form of the enzyme ( Zhang et al, 2001 ). This pathway has previously been examined in epidermal lamellar tissues from the carbohydrate overload laminitis model, where it was found to be increased at the onset of Obel grade 1 signs ( Gardner et al, 2015 ). Furthermore, lamellar tissue ERK1/2 activation, along with involvement of other signalling components, has also been observed in a dietary challenge model of laminitis and also an insulin infusion model ( Lane et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor

Baskerville

Chockalingham

Harris³

et al. 2018

PeerJ

View full text Add to dashboard Cite

BackgroundIn horses and ponies, insulin dysregulation leading to hyperinsulinemia may be associated with increased risk of laminitis, and prolonged infusion of insulin can induce the condition. It is unclear whether insulin may have a direct or indirect effect on the lamellar tissues. Insulin is structurally related to insulin-like growth factor (IGF-1), and can bind the IGF-1 receptor, albeit at a lower affinity than IGF-1.MethodsImmunohistochemistry was performed on formalin-fixed lamellar tissue sections from six normal horses, euthanised for non-research purposes, using an anti-IGF-1 receptor antibody. In further studies, lamellar epithelial cells were obtained by collagenase digestion from the hooves of 18 normal horses, also euthanised for non-research purposes, and incubated for 48 h in the presence of insulin (0–2,000 m IU/ml). The increase in cell numbers was determined using a cell proliferation assay, and compared to the effect of zero insulin using one-way ANOVA.ResultsImmunohistochemistry demonstrated IGF-1 receptors on lamellar epidermal epithelial cells. With cultured cells, insulin caused a concentration-dependent increase in cell proliferation compared to untreated cells (maximal effect 63.3 ± 12.8% more cells after 48 h with 1,000 m IU/ml insulin; P < 0.01). Co-incubation with a blocking antibody against the IGF-1 receptor significantly inhibited the proliferative effect of insulin (P < 0.01).DiscussionThese results demonstrate that IGF-1 receptors are present on lamellar epithelial cells. At high physiological concentrations, insulin may activate these cells, by a mechanism involving IGF-1 receptors, resulting in a proliferative effect. This mechanism could help to explain the link between hyperinsulinemia and laminitis.

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor

Baskerville

Chockalingham

Harris³

et al. 2018

PeerJ

View full text Add to dashboard Cite

show abstract

“…Safety in the equid is unknown but this drug or other “rapalogues” are possible therapeutic agents to be considered in future EMSAL research. However, as side effects are reported with the clinical use of these mTORC1 inhibitors , it may be important to assess more targeted inhibition of signalling downstream of this complex in the future. As RPS6 has recently been found to be a key player in epithelial disease states such as malignancies, which are characterised by some of the same cellular events likely to be important in affected lamellae in EMSAL , the discovery of unique pharmaceutical inhibitors for this protein may allow for more focused treatment of this disease in the future with fewer side effects than blocking molecules upstream in the cascades.…”

Section: Discussionmentioning

confidence: 99%

Lamellar events related to insulin‐like growth factor‐1 receptor signalling in two models relevant to endocrinopathic laminitis

Lane

Burns

Hegedus

et al. 2017

Equine Veterinary Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…Improved survival and reduced expression of JNK, NF‐ κ B, TNF‐ α and high‐mobility group box‐1 (HMGB‐1) were observed in a murine caecal ligation and puncture model (Pizzino et al ., ). JNK has been described in osmotic‐induced stress in equine spermatozoa (Garcia et al ., ), and the up‐regulation of JNK1/2 in a carbohydrate model of laminitis in horses (Gardner et al ., ). Many authors described the role of extracellular‐regulated signalling kinases 1 and 2 (ERK1/2) in LPS‐induced inflammation (Schumann et al ., ; van der Bruggen et al ., ; Roux & Blenis, ).…”

Section: Introductionmentioning

confidence: 97%

Treatment of endotoxaemia and septicaemia in the equine patient

Werners

2016

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

Endotoxins, constituents of the cell wall of gram-positive and gram-negative bacteria, regularly result in severe illness and death in horses. In endotoxaemia, these constituents are present in the systemic circulation; in septicaemia, whole microbes invade normally sterile parts of the body. Interaction of these endotoxins with pathogen recognition receptors leads to an inflammatory response that cannot always be sufficiently contained and hence needs direct treatment. Over the last decennia, our understanding of the pathophysiology of endotoxaemia and septicaemia has significantly increased. Based on improved understanding of the interaction between receptors and endotoxins as well as the subsequent downstream signalling pathways, new therapeutic targets have been identified in laboratory animal species and humans. Important species differences in the recognition of endotoxins and pathogens by their receptors as well as the inflammatory response to receptor activation hamper extrapolation of this information to the horse (and other species). Historically, horses with endotoxaemia and septicaemia have been treated mainly symptomatically and supportively. Based on the identified therapeutic targets, this review describes the current knowledge of the treatment for endotoxaemia and septicaemia in the horse with reference to the findings in other animal species and humans.

show abstract

Mitogen‐activated kinase pathway activation in epidermal lamellae in the acute stages of carbohydrate overload laminitis models and the effect of regional deep hypothermia on signalling pathways

Cited by 9 publications

References 33 publications

The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor

The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor

Lamellar events related to insulin‐like growth factor‐1 receptor signalling in two models relevant to endocrinopathic laminitis

Treatment of endotoxaemia and septicaemia in the equine patient

Contact Info

Product

Resources

About