+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Detection of endoplasmic reticulum stress and the unfolded protein response in naturally-occurring endocrinopathic equine laminitis



Detection of endoplasmic reticulum stress and the unfolded protein response in naturally-occurring endocrinopathic equine laminitis



Bmc Veterinary Research 15(1): 24



Laminitis is often associated with endocrinopathies that cause hyperinsulinemia and is also induced experimentally by hyperinsulinemia, suggesting that insulin initiates laminitis pathogenesis. Hyperinsulinemia is expected to activate pro-growth and anabolic signaling pathways. We hypothesize that chronic over-stimulation of these pathways in lamellar tissue results in endoplasmic reticulum stress, contributing to tissue pathology, as it does in human metabolic diseases. We tested this hypothesis by asking whether lamellar tissue from horses with naturally-occurring endocrinopathic laminitis showed expression of protein markers of endoplasmic reticulum stress. Three markers of endoplasmic reticulum stress, spliced XBP1, Grp78/BiP and Grp94, were upregulated 2.5-9.5 fold in lamellar tissues of moderately to severely laminitic front limbs (n = 12) compared to levels in controls (n = 6-7) measured by immunoblotting and densitometry. Comparing expression levels between laminitic front limbs and less affected hind limbs from the same horses (paired samples from 7 to 8 individual horses) demonstrated significantly higher expression for both spliced XBP1 and Grp78/BiP in the laminitic front limbs, and a similar trend for Grp94. Expression levels of the 3 markers were minimal in all samples of the control (n = 6-7) or hind limb groups (n = 7-8). Immunofluorescent localizations were used to identify cell types expressing high levels of Grp78/BiP, as an indicator of endoplasmic reticulum stress. Grp78/BiP expression was highly elevated in suprabasal epidermal keratinocytes and only observed in laminitic front limbs (10/12 laminitic samples, compared to 0/7 in sections from the hind limbs and 0/5 of controls). These data demonstrate that the endoplasmic reticulum stress pathway is active in naturally occurring cases of laminitis and is most active within a subset of epidermal keratinocytes. These data provide the rationale for further study of endoplasmic reticulum stress in experimental models of laminitis and the links between laminitis and human diseases sharing activation of this stress pathway. Pharmacological options to manipulate the endoplasmic reticulum stress pathway under investigation for human disease could be applicable to laminitis treatment and prevention should this pathway prove to be a driver of disease progression.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 066443655

Download citation: RISBibTeXText

PMID: 30630474

DOI: 10.1186/s12917-018-1748-x


Related references

Endoplasmic reticulum stress and the unfolded protein response. Clinics in Liver Disease 13(4): 581-590, 2009

Endoplasmic reticulum stress: signaling the unfolded protein response. Physiology 22: 193-201, 2007

Endoplasmic reticulum stress sensing in the unfolded protein response. Cold Spring Harbor Perspectives in Biology 5(3): A013169, 2013

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in plants. Protoplasma 253(3): 753-764, 2016

The unfolded protein response--a stress signaling pathway of the endoplasmic reticulum. Journal of Chemical Neuroanatomy 28(1-2): 79-92, 2004

The role of endoplasmic reticulum stress and the unfolded protein response in fibrosis. Current Opinion in Rheumatology 24(6): 663-668, 2013

The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Atherosclerosis. International Journal of Molecular Sciences 17(2), 2016

Methods for monitoring endoplasmic reticulum stress and the unfolded protein response. International Journal of Cell Biology 2010: 830307, 2010

Cellular response to endoplasmic reticulum stress mediated by unfolded protein response pathway. Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme 44(15 Suppl): 2442-2448, 1999

Severe injury is associated with insulin resistance, endoplasmic reticulum stress response, and unfolded protein response. Annals of Surgery 255(2): 370-378, 2012

Endoplasmic reticulum stress and the unfolded protein response in disorders of myelinating glia. Brain Research 1648(Pt B): 594-602, 2016

Assessment of endoplasmic reticulum stress and the unfolded protein response in endothelial cells. Methods in Enzymology 489: 127-146, 2011

A molecular mechanism for glaucoma: endoplasmic reticulum stress and the unfolded protein response. Trends in Molecular Medicine 19(10): 586-593, 2014

Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death and Differentiation 14(9): 1576-1582, 2007

Endoplasmic reticulum stress and unfolded protein response in inflammatory bowel disease. Inflammatory Bowel Diseases 21(3): 636-644, 2015