Presented in part at the 2nd Annual AAEP Foundation Equine Laminitis Research Workshop. West Palm Beach, Florida, November 2009 and the 5th International Laminitis Conference, West Palm Beach, Florida, October 2011
Laminar Regulation of STAT1 and STAT3 in Black Walnut Extract and Carbohydrate Overload Induced Models of Laminitis
Article first published online: 13 JUL 2012
Copyright © 2012 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 26, Issue 4, pages 996–1004, July-August 2012
How to Cite
Leise, B.S., Watts, M., Tanhoff, E., Johnson, P.J., Black, S.J. and Belknap, J.K. (2012), Laminar Regulation of STAT1 and STAT3 in Black Walnut Extract and Carbohydrate Overload Induced Models of Laminitis. Journal of Veterinary Internal Medicine, 26: 996–1004. doi: 10.1111/j.1939-1676.2012.00944.x
- Issue published online: 13 JUL 2012
- Article first published online: 13 JUL 2012
- Manuscript Accepted: 10 MAR 2012
- Manuscript Revised: 8 NOV 2011
- Manuscript Received: 14 FEB 2011
- U.S. Equestrian Federation. Grant Number: EHRF 2009-1
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.
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.
Archived laminar tissue from horses.
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.
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 and Clinical Relevance
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.