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.
Abstract: In sepsis models, mitogen-activated protein kinases (MAPKs) are reported to incite inflammatory injury to tissues and are purported to be a therapeutic target. Objective: To assess MAPK signalling in lamellae in sepsis-related laminitis (SRL) at different time points after induction of laminitis via carbohydrate overload, and to determine the effect of regional deep hypothermia (RDH) on MAPK signalling. Methods: In vitro study using archived tissue samples. Methods: Lamellar concentrations of MAPKs were assessed in archived lamellar samples from 2 studies: 1) the starch gruel model of SRL with 3 groups (n = 6/group) of horses (control, onset of fever [DEV] Obel Grade 1 lameness [OG1]); and 2) from limbs maintained at ambient (AMB) and hypothermic (ICE) temperatures (n = 6/group) in animals given a bolus of oligofructose. Immunoblotting and immunolocalisation were used to assess lamellar concentrations and cellular localisation of total and activated (phosphorylated) forms of p38 MAPK, extracellular-regulated kinase (ERK) 1/2, and stress-activated protein kinase/c-jun N terminal kinase (SAPK/JNK) 1/2. Results: Lamellar samples had statistically significant increased concentrations of activated ERK 1/2 at the onset of OG1 laminitis (vs. control) in the starch gruel model, but showed no significant change between ICE and AMB limbs in the RDH model. Phospho-SAPK/JNK 1/2 exhibited a similar significant increase in the OG1 samples, but was also increased in ICE (vs. AMB) limbs. No statistically significant changes in lamellar p38 MAPK concentrations were noted. Conclusions: Increased concentrations of activated ERK 1/2 and SAPK/JNK in the acute stages of SRL indicate a possible role of these signalling proteins in lamellar injury. Signalling related to ERK 1/2 and SAPK/JNK 1/2 pathways should be further investigated to determine if these play a detrimental role in laminitis and may be therapeutic targets to be manipulated independently of RDH.
© 2015 EVJ Ltd.
Publication Date: 2015-08-29 PubMed ID: 26222495DOI: 10.1111/evj.12488Google Scholar: Lookup
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- Journal Article
Summary
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The research article investigates the role of certain proteins in the early stages of a hoof disease called laminitis, caused by carbohydrate overload in horses. It also looks at the impact of regional deep hypothermia on these proteins.
Overview of the Study
- The study focused on proteins known as mitogen-activated protein kinases (MAPKs), which are known to cause inflamatory injuries in sepsis cases.
- The researchers aimed to observe the behavior of these proteins in instances of sepsis-related laminitis (SRL) at different stages following the initiation of the disease through carbohydrate overload.
- They also sought to understand the effects of regional deep hypothermia (RDH)––a cooling treatment–– on these proteins’ activities.
Methodology
- An in vitro study was conducted using archived tissue samples. Lamellar samples – the tissue from the horses’ hooves – were obtained from two separate studies.
- One study examined a starch gruel model of SRL, with multiple groups of horses at different stages of the disease, ranging from control group to early-stage disease.
- The second study focused on limbs at varying temperatures (ambient and hypothermic) in animals who had been fed a carbohydrate-rich diet.
- Both studies used immunoblotting and immunolocalization techniques to examine the concentrations and locations of the proteins.
Results
- The researchers found a significant increase in the activated forms of two types of MAPK proteins (ERK 1/2 and SAPK/JNK 1/2) during the early stages of the disease.
- This increased concentration suggests that these proteins could play a significant role in the tissue damage seen in laminitis.
- However, the hypothermia treatment didn’t significantly change these proteins’ activities or concentrations, indicating that this treatment might not be effective for modulating these particular proteins.
Conclusions and Future Research
- The research indicates that the activated ERK 1/2 and SAPK/JNK 1/2 pathways potentially contribute to the early stages of laminitis, suggesting a new avenue of research for understanding and treating this disease.
- Further studies are recommended to validate these results and examine whether interfering with these proteins could serve as a new therapeutic technique, separate from hypothermia treatment.
Cite This Article
APA
Gardner AK, Kelly CS, van Eps AW, Burns TA, Watts MR, Belknap JK.
(2015).
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.
Equine Vet J, 48(5), 633-640.
https://doi.org/10.1111/evj.12488 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, USA.
- School of Veterinaary Science, University of Queensland, Australia.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, USA.
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, USA.
MeSH Terms
- Animals
- Cold Temperature
- Dietary Carbohydrates / adverse effects
- Epidermis
- Foot Diseases / chemically induced
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Hoof and Claw / metabolism
- Hoof and Claw / pathology
- Horse Diseases / chemically induced
- Horse Diseases / metabolism
- Horses
- Inflammation / chemically induced
- Inflammation / metabolism
- Inflammation / veterinary
- MAP Kinase Signaling System / physiology
- Mitogen-Activated Protein Kinases / genetics
- Mitogen-Activated Protein Kinases / metabolism
Citations
This article has been cited 3 times.- Smith EJ, Beaumont RE, McClellan A, Sze C, Palomino Lago E, Hazelgrove L, Dudhia J, Smith RKW, Guest DJ. Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors.. Cell Tissue Res 2023 Mar;391(3):523-544.
- Roszkowska K, Witkowska-Pilaszewicz O, Przewozny M, Cywinska A. Whole body and partial body cryotherapies - lessons from human practice and possible application for horses.. BMC Vet Res 2018 Dec 12;14(1):394.
- Baskerville CL, Chockalingham S, Harris PA, Bailey SR. The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor.. PeerJ 2018;6:e5945.
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