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Decreased expression of p63, a regulator of epidermal stem cells, in the chronic laminitic equine hoof.
Abstract: Abnormal epidermal stem cell regulation may contribute to the pathogenesis of equine chronic laminitis. Objective: To analyse the involvement of p63, a regulator of epidermal stem cell proliferative potential, in chronic laminitis. Methods: Epidermal tissues from skin, coronet and lamellae of the dorsal foot were harvested from 5 horses with chronic laminitis and 5 control horses. Tissues were analysed using histopathology, immunofluorescence microscopy and quantitative immunoblotting. Results: Hoof lamellae of laminitic horses had a lower frequency of p63 positive cells than control lamellae, particularly in the distal region. Quantitative immunoblotting confirmed reduced p63 expression in the laminitic distal lamellar region. The decreased p63 expression in laminitic epidermal lamellae was most apparent in the abaxial region adjacent to the hoof wall and highly associated with the formation of terminally differentiated, dysplastic and hyperkeratotic epidermis in this region, whereas lamellae from control horses maintained high p63 expression throughout the axial-abaxial axis. Conclusions: Expression of p63 in equine skin resembles that reported in other species, including man and rodents, suggesting that p63 can serve as a marker for the proliferative potential of equine epidermal stem cells. p63 expression was significantly lower in the chronic laminitic hoof than in that of control horses, suggesting laminitic hoof epithelium has more limited proliferative potential with a shift towards differentiation. This may reflect reduced activity of epidermal stem cells in laminitic hoof. It is proposed that p63 contributes to the maintenance of hoof lamellae and that misregulation of p63 expression may lead to epidermal dysplasia during lamellar wedge formation. Conclusions: This study suggests that loss of epidermal stem cells contributes to the pathogenesis of equine laminitis. Autologous transplantation of p63-positive epidermal stem cells from unaffected regions may have regenerative therapeutic potential for laminitic horses.
© 2011 EVJ Ltd.
Publication Date: 2011-03-11 PubMed ID: 21496086DOI: 10.1111/j.2042-3306.2010.00325.xGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research explores how reduced activity in a regulatory gene of epidermal stem cells, p63, might contribute to the hoof disease known as equine chronic laminitis.
Objective & Methods
- The researchers set out to investigate the relationship between the regulator of epidermal stem cell proliferative potential, known as p63, and a hoof condition in horses called chronic laminitis.
- The team gathered and analyzed epidermal tissues from the skin, coronet, and lamellae of the dorsal foot of both healthy horses and horses suffering from chronic laminitis. The methods used included histopathology, immunofluorescence microscopy, and quantitative immunoblotting.
Results
- Laminitic horses showed a lower count of p63 positive cells in their hoof lamellae, especially in the distal region.
- This lowered expression of p63 in the laminitic distal lamellar region was verified through quantitative immunoblotting.
- The reduction in p63 expression was most pronounced in the abaxial region next to the hoof wall. This was significantly related to the formation of terminally differentiated, dysplastic, and hyperkeratotic epidermis in this area.
- In contrast to that, control horses displayed high p63 expression throughout the axial-abaxial axis.
Conclusions
- The p63 expression in horses was found to be similar to that in humans and rodents, hinting that it can serve as a marker for the proliferative potential of equine epidermal stem cells.
- The chronic laminitic hoof showed significantly lower p63 expression, implying that laminitic hoof epithelium has a lesser tendency to proliferate, with a shift towards differentiation. This could reflect a decrease in the activity of epidermal stem cells in laminitic hoof.
- It was suggested that p63 plays a role in maintaining hoof lamellae, and that its misregulation may lead to epidermal dysplasia during lamellar wedge formation.
Implications of the Study
- The study indicates that a loss of epidermal stem cells may contribute to the development of equine laminitis.
- The researchers propose that transplanting p63-positive epidermal stem cells from unaffected areas could potentially serve as a regenerative treatment for horses afflicted with laminitis.
Cite This Article
APA
Carter RA, Engiles JB, Megee SO, Senoo M, Galantino-Homer HL.
(2011).
Decreased expression of p63, a regulator of epidermal stem cells, in the chronic laminitic equine hoof.
Equine Vet J, 43(5), 543-551.
https://doi.org/10.1111/j.2042-3306.2010.00325.x Publication
Researcher Affiliations
- Laminitis Institute, Department of Clinical Studies/New Bolton Center, University of Pennsylvania School of Veterinary Medicine, PA, USA.
MeSH Terms
- Animals
- Chronic Disease
- Female
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Gene Expression Regulation
- Hoof and Claw / metabolism
- Horse Diseases / metabolism
- Horses
- Inflammation / metabolism
- Inflammation / veterinary
- Male
- Tumor Suppressor Proteins / genetics
- Tumor Suppressor Proteins / metabolism
Citations
This article has been cited 7 times.- Cequier A, Sanz C, Rodellar C, Barrachina L. The Usefulness of Mesenchymal Stem Cells beyond the Musculoskeletal System in Horses. Animals (Basel) 2021 Mar 25;11(4).
- Cassimeris L, Engiles JB, Galantino-Homer H. Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis. PLoS One 2020;15(12):e0232920.
- Armstrong C, Cassimeris L, Da Silva Santos C, Micoogullari Y, Wagner B, Babasyan S, Brooks S, Galantino-Homer H. The expression of equine keratins K42 and K124 is restricted to the hoof epidermal lamellae of Equus caballus. PLoS One 2019;14(9):e0219234.
- Cassimeris L, Engiles JB, Galantino-Homer H. Detection of endoplasmic reticulum stress and the unfolded protein response in naturally-occurring endocrinopathic equine laminitis. BMC Vet Res 2019 Jan 10;15(1):24.
- Linardi RL, Megee SO, Mainardi SR, Senoo M, Galantino-Homer HL. Expression and localization of epithelial stem cell and differentiation markers in equine skin, eye and hoof. Vet Dermatol 2015 Aug;26(4):213-e47.
- Suzuki D, Sahu R, Leu NA, Senoo M. The carboxy-terminus of p63 links cell cycle control and the proliferative potential of epidermal progenitor cells. Development 2015 Jan 15;142(2):282-90.
- Steelman SM, Chowdhary BP. Plasma proteomics shows an elevation of the anti-inflammatory protein APOA-IV in chronic equine laminitis. BMC Vet Res 2012 Sep 27;8:179.
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