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, A.K., Kelly, C.S., van Eps, A.W., Burns, T.A., Watts, M.R. and Belknap, J.K. (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 Veterinary Journal, 48 5: 633-640. doi:10.1111/evj.12488


Author Gardner, A.K.
Kelly, C.S.
van Eps, A.W.
Burns, T.A.
Watts, M.R.
Belknap, J.K.
Title 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
Journal name Equine Veterinary Journal   Check publisher's open access policy
ISSN 2042-3306
0425-1644
Publication date 2015-08-29
Year available 2015
Sub-type Article (original research)
DOI 10.1111/evj.12488
Open Access Status Not Open Access
Volume 48
Issue 5
Start page 633
End page 640
Total pages 8
Place of publication Hoboken, New Jersey, United States
Publisher John Wiley & Sons
Collection year 2016
Language eng
Formatted abstract
Reasons for performing study: In sepsis models, mitogen-activated protein kinases (MAPKs) are reported to incite inflammatory injury to tissues and are purported to be a therapeutic target.

Objectives: 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.

Study design: 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.
Keyword Horse
Digital lamellae
Laminitis
Sepsis
Inflammation
Mitogen-activated protein kinase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Veterinary Science Publications
 
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