Laminar regulation of STAT1 and STAT3 in black walnut extract and carbohydrate overload induced models of laminitis.
Abstract: STAT1 and STAT3 are important signaling molecules in disorders of systemic inflammation and are likely to be involved in laminitis, as laminar and systemic inflammation have been well documented in experimental models of laminitis. Objective: The STAT1 and STAT3 activation (via phosphorylation of tyrosine and serine moieties) is occurring in the laminar tissue during the developmental and onset of lameness time points in both the black walnut extract (BWE) and carbohydrate overload (CHO) models of laminitis. Methods: Archived laminar tissue from horses. Methods: Experimental studies of induced laminitis (BWE and CHO administration) in horses were conducted and laminar tissue samples archived. Western hybridization was performed to determine concentrations of Tyr- and Ser-phosphorylated STAT1 and STAT3 from these archived samples. The RT-qPCR was also performed to assess mRNA concentrations of target genes of STAT1 and STAT3. Results: Increases (P < .05) in phosphorylation of tyrosine705 and serine727 of STAT3, demonstrated by band intensity ratios, are present in laminar tissue from both the BWE and CHO models at the DEV and OG1 time points. No change in phosphorylation of tyrosine701 or serine727 of STAT1 was present in the laminar tissue from either the BWE or the CHO models. The SOCS3 mRNA concentrations were increased at the onset of lameness in both the CHO and BWE models. Conclusions: The STAT3 activation likely plays a role in equine laminitis, similar to its reported involvement in organ injury/failure in human sepsis. Regulation of JAK-STAT, through STAT3 inhibitors, might serve as potential therapeutic target for controlling the inflammatory response in the septic horse.
Copyright © 2012 by the American College of Veterinary Internal Medicine.
Publication Date: 2012-07-19 PubMed ID: 22805114DOI: 10.1111/j.1939-1676.2012.00944.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the role of STAT1 and STAT3 signaling molecules in inflammation disorders and their potential involvement in laminitis, a painful condition affecting horses. The study specifically examines how these molecules are activated in two models of laminitis: induced by black walnut extract (BWE) and carbohydrate overload (CHO). The results suggest that STAT3 activation may be significant in equine laminitis and could be a potential target for therapeutic intervention.
Understanding STAT1 and STAT3
- STAT1 and STAT3 are signaling molecules that play vital roles in inflammation disorders.
- Laminitis, an inflammation condition in horses, has been associated with systemic inflammation, suggesting a potential role for these molecules in the condition.
The Study Models
- The researchers used two models of induced laminitis in horses: one caused by black walnut extract (BWE) and another by carbohydrate overload (CHO).
- Laminar tissue samples from these models were archived for further analysis.
Testing Processes
- Western hybridization was conducted to determine concentrations of Tyr- and Ser-phosphorylated STAT1 and STAT3 in the collected samples.
- The researchers also performed RT-qPCR to assess mRNA concentrations of target genes of STAT1 and STAT3.
Results of the Study
- The researchers detected significant increases in phosphorylation of tyrosine705 and serine727 of STAT3 in both the BWE and CHO models at specific time points.
- No change in phosphorylation of tyrosine701 or serine727 of STAT1 was found in either model.
- The concentrations of SOCS3 mRNA were found to increase at the onset of lameness in both the CHO and BWE models.
Conclusions and Implications
- Results suggest that the activation of STAT3 may play an important role in equine laminitis.
- This finding presents potential means for controlling the inflammation response in horses with sepsis, as the regulation of JAK-STAT, through STAT3 inhibitors, could serve as a therapeutic target.
Cite This Article
APA
Leise BS, Watts M, Tanhoff E, Johnson PJ, Black SJ, Belknap JK.
(2012).
Laminar regulation of STAT1 and STAT3 in black walnut extract and carbohydrate overload induced models of laminitis.
J Vet Intern Med, 26(4), 996-1004.
https://doi.org/10.1111/j.1939-1676.2012.00944.x Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
MeSH Terms
- Animals
- Blotting, Western
- Disease Models, Animal
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Horse Diseases / metabolism
- Horses
- Immunohistochemistry / veterinary
- Inflammation / metabolism
- Inflammation / veterinary
- Lameness, Animal / genetics
- Lameness, Animal / metabolism
- Phosphorylation
- RNA, Messenger / biosynthesis
- RNA, Messenger / genetics
- Real-Time Polymerase Chain Reaction / veterinary
- Retrospective Studies
- STAT1 Transcription Factor / biosynthesis
- STAT1 Transcription Factor / genetics
- STAT1 Transcription Factor / metabolism
- STAT3 Transcription Factor / biosynthesis
- STAT3 Transcription Factor / genetics
- STAT3 Transcription Factor / metabolism
- Statistics, Nonparametric
Citations
This article has been cited 4 times.- Burns TA, Watts MR, Belknap JK, van Eps AW. Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing. J Vet Intern Med 2023 Mar;37(2):681-688.
- Watts MR, Hegedus OC, Eades SC, Belknap JK, Burns TA. Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light-breed horses. J Vet Intern Med 2019 May;33(3):1483-1492.
- Dern K, van Eps A, Wittum T, Watts M, Pollitt C, Belknap J. Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model. J Vet Intern Med 2018 Jan;32(1):450-458.
- Leise BS, Watts MR, Roy S, Yilmaz AS, Alder H, Belknap JK. Use of laser capture microdissection for the assessment of equine lamellar basal epithelial cell signalling in the early stages of laminitis. Equine Vet J 2015 Jul;47(4):478-88.
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