Continuous digital hypothermia reduces expression of keratin 17 and 1L-17A inflammatory pathway mediators in equine laminitis induced by hyperinsulinemia

Cassimeris, Lynne; Armstrong, Caren; Burger, Quinnlyn C.; Stokes, Simon M.; Eps, A. W. van; Galantino‐Homer, Hannah

doi:10.1016/j.vetimm.2021.110326

Cited by 6 publications

(3 citation statements)

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“…In other systems, ischemia and blunt tissue trauma are important mechanisms for induction of sterile inflammation and local/regional elaboration of damage‐associated molecular patterns (DAMPs); IL‐17A signaling has been shown to be a central mediator of both acute and chronic inflammatory conditions, particularly those associated with sterile inflammation and ischemia (such as trauma, surgical wounds, and ischemia/reperfusion injury secondary to organ transplant). 34 Studies of IL‐17A signaling and its role in naturally occurring 14 and experimental 35 equine laminitis of various types provide even more support that this mechanism is active in developmental and late stage‐disease; IL‐17A‐associated inflammatory signaling might be central to the pathology of diverse forms of laminitis. Inhibition of IL‐17A signaling (both genetically and pharmacologically) has improved outcomes in animal models and human patients with various acute and chronic diseases, including psoriasis (which, along with equine laminitis, represents an epidermal disease that highlights the importance of inflammatory signaling in the regulation of keratinocyte differentiation, maturation, and function); similar approaches could be shown useful in the treatment and prevention of equine laminitis in the future.…”

Section: Discussionmentioning

confidence: 99%

“…In other systems, ischemia and blunt tissue trauma are important mechanisms for induction of sterile inflammation and local/regional elaboration of damage-associated molecular patterns (DAMPs); IL-17A signaling has been shown to be a central mediator of both acute and chronic inflammatory conditions, particularly those associated with sterile inflammation and ischemia (such as trauma, surgical wounds, and ischemia/reperfusion injury secondary to organ transplant). 34 Studies of IL-17A signaling and its role in naturally occurring 14 and experimental 35 Along with ischemia, excessive mechanical stretch seems to be inevitable in the development of SLL. Results of histologic examination of lamellar tissue from the animals used in this study are published, 6 as well from animals used in a separate study utilizing the same model (albeit for a shorter period of time, 48 hours).…”

Section: Discussionmentioning

confidence: 99%

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Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing

Burns

Watts

Belknap

et al. 2023

Veterinary Internal Medicne

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Background Supporting limb laminitis (SLL) is a complication of severe orthopedic disease in horses and is often life‐limiting, yet the pathophysiology remains obscure. Hypothesis/Objectives To investigate the role of digital lamellar inflammatory signaling in the pathophysiology of SLL using a model of unilateral weight bearing, hypothesizing that there would be evidence of lamellar inflammation in limbs subjected to the model. Animals Thirteen healthy adult Standardbred horses were used for this study (11 geldings, 2 mares; mean age 6.5 ± 2.5 years; mean body weight 458.3 ± 32.8 kg). Methods Randomized controlled experimental study. A steel shoe with a custom insert was applied to a randomly selected front foot of 7 horses; 6 horses were unshod and served as controls. After 92 hours, all horses were humanely euthanized, and digital lamellar samples were collected. Lamellar protein and mRNA were isolated and used to perform western blot and PCR. Results Lamellar concentrations of IL‐6 mRNA were higher in SL tissue than IL HIND tissue (median [25%‐75%] normalized copy number 191 [111‐3060] and 48 [25‐74], respectively; P=.003), and lamellar concentrations of COX‐2 mRNA were higher in SL tissue than CON tissue (normalized copy number 400 [168‐634] and 125 [74‐178], respectively; P=.007). Lamellar concentrations of IL‐1B, IL‐10, and COX‐1 mRNA were not significantly different between groups. The concentrations of phosphorylated (activated) STAT1 and STAT3 proteins were higher in SL (0.5 [0.35‐0.87] and 1.35 [1.1‐1.7], respectively) compared to CON (0.24 [0.09‐0.37] and 0.31 [0.16‐037]) and UL HIND (0.27 [0.19‐0.37] and 0.38 [0.24‐0.5]); P=0.01 and P<0.001. Conclusions and Clinical Importance Lamellar inflammatory signaling was higher in tissue from horses subjected to prolonged unilateral weight‐bearing, suggesting that these pathways could be relevant to the pathophysiology of SLL.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing

Burns

Watts

Belknap

et al. 2023

Veterinary Internal Medicne

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“…In both the Krt90 whnl mutant mice and horses with laminitis, these lesions can progress to partial or complete sloughing of the nail unit [ 16 , 51 ]. Equine laminitis is also characterized by increased KRT17 expression [ 53 ] and abnormal localization of KRT14, which is normally restricted to the basal cell layer of the equine nail bed [ 54 , 55 ]. The similarities in these lesions suggest that, in spite of the difference in initiating cause, several subsequent aspects of equine laminitis pathogenesis may be modeled by the Krt90 whnl mutant mouse.…”

Section: Discussionmentioning

confidence: 99%

Witch Nails (Krt90whnl): A spontaneous mouse mutation affecting nail growth and development

et al. 2022

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Numerous single gene mutations identified in humans and mice result in nail deformities with many similarities between the species. A spontaneous, autosomal, recessive mutation called witch nails (whnl) is described here where the distal nail matrix and nail bed undergo degenerative changes resulting in formation of an abnormal nail plate causing mice to develop long, curved nails. This mutation arose spontaneously in a colony of MRL/MpJ-Faslpr/J at The Jackson Laboratory. Homozygous mutant mice are recognizable by 8 weeks of age by their long, curved nails. The whnl mutation, mapped on Chromosome 15, is due to a 7-bp insertion identified in the 3’ region of exon 9 in the Krt90 gene (formerly Riken cDNA 4732456N10Rik), and is predicted to result in a frameshift that changes serine 476 to arginine and subsequently introduces 36 novel amino acids into the protein before a premature stop codon (p. Ser476ArgfsTer36). By immunohistochemistry the normal KRT90 protein is expressed in the nail matrix and nail bed in control mice where lesions are located in mutant mice. Immunoreactivity toward equine KRT124, the ortholog of mouse KRT90, is restricted to the hoof lamellae (equine hoof wall and lamellae are homologous to the mouse nail plate and nail bed) and the mouse nail bed. Equine laminitis lesions are similar to those observed in this mutant mouse suggesting that the latter may be a useful model for hoof and nail diseases. This first spontaneous mouse mutation affecting the novel Krt90 gene provides new insight into the normal regulation of the molecular pathways of nail development.

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Continuous digital hypothermia for prevention and treatment of equine acute laminitis: A practical review

Lavado

Lewis

Montgomery

2023

The Veterinary Journal

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Continuous digital hypothermia reduces expression of keratin 17 and 1L-17A inflammatory pathway mediators in equine laminitis induced by hyperinsulinemia

Cited by 6 publications

References 45 publications

Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing

Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing

Witch Nails (Krt90whnl): A spontaneous mouse mutation affecting nail growth and development

Continuous digital hypothermia for prevention and treatment of equine acute laminitis: A practical review

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