Overexpression of eCLCA1 in small airways of horses with recurrent airway obstruction.
Abstract: The human hCLCA1 and murine mCLCA3 (chloride channels, calcium-activated) have recently been identified as promising therapeutic targets in asthma. Recurrent airway obstruction in horses is an important animal model of human asthma. Here, we have cloned and characterized the first equine CLCA family member, eCLCA1. The 913 amino acids eCLCA1 polypeptide forms a 120-kDa transmembrane glycoprotein that is processed to an 80-kDa protein in vivo. Three single nucleotide polymorphisms were detected in the eCLCA1 coding region in 14 horses, resulting in two amino acid changes (485H/R and 490V/L). However, no functional differences were recorded between the channel properties of the two variants in transfected HEK293 cells. The eCLCA1 protein was detected immunohistochemically in mucin-producing cells in the respiratory and intestinal tracts, cutaneous sweat glands, and renal mucous glands. Strong overexpression of eCLCA1 was observed in the airways of horses with recurrent airway obstruction using Northern blot hybridization, Western blotting, immunohistochemistry, and real-time quantitative RT-PCR. The results suggest that spontaneous or experimental recurrent airway obstruction in horses may serve as a model to study the role of CLCA homologs in chronic airway disease with overproduction of mucins.
Publication Date: 2005-05-06 PubMed ID: 15879574PubMed Central: PMC1383431DOI: 10.1369/jhc.4A6599.2005Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
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- Non-U.S. Gov't
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- U.S. Gov't
- P.H.S.
Summary
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The research article discusses a study which found a high level of eCLCA1 (a type of chloride channel) in small airways of horses suffering from recurrent airway obstruction. This discovery presents a potential for exploring these molecular pathways as therapeutic targets for chronic respiratory diseases such as asthma.
eCLCA1 and its Role in Respiratory Diseases
- The researchers identified and characterized the equine CLCA (chloride channels, calcium-activated) family member, eCLCA1, known to play a role in mucous production and potentially inflammatory responses in certain respiratory diseases.
- Previous studies had identified the human hCLCA1 and murine mCLCA3 proteins, a family member of eCLCA1, as potential therapeutic targets in asthma treatment. By studying eCLCA1 in horses, they hoped to gain insights that can be translated into human health applications.
Studying eCLCA1 Variants
- Three variations of the eCLCA1 protein, caused by single nucleotide polymorphisms in the protein coding area, were found in 14 horses. These variations resulted in two different forms of the eCLCA1 protein, which differed by two amino acids.
- However, no significant differences in function were recorded between the two eCLCA1 variants, when they were inserted into HEK293 cells (a type of human cell line commonly used in scientific experiments).
eCLCA1 Overexpression in Horses with Recurrent Airway Obstruction
- The research discovered high levels of the eCLCA1 protein in horses suffering from recurrent airway obstruction, a condition similar to human asthma. This was observed through several methods: Northern blot hybridization, Western blotting, immunohistochemistry, and real-time quantitative RT-PCR.
- eCLCA1 was found to be primarily present in mucin-producing cells in the respiratory and intestinal tracts, sweat glands of the skin, and mucous glands in the kidneys.
- The high presence of eCLCA1 in horses with recurrent airway obstruction suggests that there may be a correlation between this protein and chronic respiratory diseases, opening the potential to further investigate its role in the pathophysiology of these conditions.
Implications for Future Research
- The findings of this study suggest that horses with spontaneous or experimental recurrent airway obstruction could serve as an animal model to investigate the role of CLCA proteins in human chronic airway illnesses.
- By understanding more about the role and mechanisms of these chloride channels in respiratory diseases, new preventative or therapeutic targets could potentially be developed for conditions like asthma, which are marked by overproduction of mucins and inflammation in the airways.
Cite This Article
APA
Anton F, Leverkoehne I, Mundhenk L, Thoreson WB, Gruber AD.
(2005).
Overexpression of eCLCA1 in small airways of horses with recurrent airway obstruction.
J Histochem Cytochem, 53(8), 1011-1021.
https://doi.org/10.1369/jhc.4A6599.2005 Publication
Researcher Affiliations
- Department of Pathology, School of Veterinary Medicine Hannover, Hannover, Germany.
MeSH Terms
- Airway Obstruction / metabolism
- Amino Acid Sequence
- Animals
- Bronchi / metabolism
- Cell Line
- Chloride Channels / biosynthesis
- Chloride Channels / genetics
- Disease Models, Animal
- Horses
- Humans
- Molecular Sequence Data
- Organ Specificity
- Phylogeny
- Polymorphism, Single Nucleotide
- RNA, Messenger / biosynthesis
- Recurrence
- Transfection
- Up-Regulation
Grant Funding
- R01 EY010542 / NEI NIH HHS
- R29 EY010542 / NEI NIH HHS
- EY-10542 / NEI NIH HHS
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Citations
This article has been cited 13 times.- Bartenschlager F, Klymiuk N, Weise C, Kuropka B, Gruber AD, Mundhenk L. Evolutionarily conserved properties of CLCA proteins 1, 3 and 4, as revealed by phylogenetic and biochemical studies in avian homologues. PLoS One 2022;17(4):e0266937.
- Liu CL, Shi GP. Calcium-activated chloride channel regulator 1 (CLCA1): More than a regulator of chloride transport and mucus production. World Allergy Organ J 2019 Nov;12(11):100077.
- Mundhenk L, Erickson NA, Klymiuk N, Gruber AD. Interspecies diversity of chloride channel regulators, calcium-activated 3 genes. PLoS One 2018;13(1):e0191512.
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