Laminar regulation of STAT1 and STAT3 in black walnut extract and carbohydrate overload induced models of laminitis.

IF 2.6 2区 农林科学
B S Leise, M Watts, E Tanhoff, P J Johnson, S J Black, J K Belknap
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引用次数: 20

Abstract

Background: 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.

Hypothesis: 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.

Animals: 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 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.

STAT1和STAT3在黑核桃提取物和碳水化合物超载诱导的板膜炎模型中的层流调节。
背景:STAT1和STAT3是全身性炎症紊乱的重要信号分子,可能参与了层流和全身性炎症,层流和全身性炎症已经在层流炎的实验模型中得到了充分的记录。假设:在黑核桃提取物(BWE)和碳水化合物过载(CHO)的板层炎模型中,STAT1和STAT3的激活(通过酪氨酸和丝氨酸部分的磷酸化)发生在板层组织的发育和跛行时间点。动物:马的存档层状组织。方法:对马进行了诱导性板层炎(BWE和CHO)的实验研究,并存档了板层组织样本。Western杂交测定这些存档样品中Tyr和ser磷酸化的STAT1和STAT3的浓度。RT-qPCR检测STAT1和STAT3靶基因mRNA浓度。结论和临床意义:STAT3激活可能在马的板炎中起作用,类似于其在人类败血症中参与器官损伤/衰竭的报道。通过STAT3抑制剂调控JAK-STAT,可能成为控制脓毒症马炎症反应的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine Veterinary-General Veterinary
自引率
11.50%
发文量
243
期刊介绍: The mission of the Journal of Veterinary Internal Medicine is to advance veterinary medical knowledge and improve the lives of animals by publication of authoritative scientific articles of animal diseases.
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