Home LiteratureArticle Details
PMID: 18954282 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

The role of CLCA proteins in inflammatory airway disease.

Annual review of physiology ·Vol. 71 ·2009-00-00 ·Pages 425-49

Patel AC, Brett TJ, Holtzman MJ

Abstract

Inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) exhibit stereotyped traits that are variably expressed in each person. In experimental mouse models of chronic lung disease, these individual disease traits can be genetically segregated and thereby linked to distinct determinants. Functional genomic analysis indicates that at least one of these traits, mucous cell metaplasia, depends on members of the calcium-activated chloride channel (CLCA) gene family. Here we review advances in the biochemistry of the CLCA family and the evidence of a role for CLCA family members in the development of mucous cell metaplasia and possibly airway hyperreactivity in experimental models and in humans. On the basis of this information, we develop the model that CLCA proteins are not integral membrane proteins with ion channel function but instead are secreted signaling molecules that specifically regulate airway target cells in healthy and disease conditions.

MeSH Terms
Amino Acid Sequence Animals Asthma/physiopathology Chloride Channels/analysis,genetics,physiology Disease Models, Animal Humans Mice Molecular Sequence Data Pulmonary Disease, Chronic Obstructive/physiopathology Respiratory Mucosa/physiology
Chemicals
Chloride Channels
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Patel Anand C
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Brett Tom J
Holtzman Michael J
References (135)
135 references, click to expand
  1. Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine.
    J Biol Chem. 2004 Oct 1;279(40):41792-800 PMID: 15284223
  2. Re-expression of detachment-inducible chloride channel mCLCA5 suppresses growth of metastatic breast cancer cells.
    J Biol Chem. 2004 Oct 1;279(40):41634-41 PMID: 15292178
  3. Association of the hCLCA1 gene with childhood and adult asthma.
    Genes Immun. 2004 Nov;5(7):540-7 PMID: 15318163
  4. Primary respiratory syncytial virus infection in mice.
    J Med Virol. 1988 Oct;26(2):153-62 PMID: 3183639
  5. Autosomal recessive inheritance of airway hyperreactivity to 5-hydroxytryptamine.
    J Appl Physiol (1985). 1989 Sep;67(3):1125-32 PMID: 2793705
  6. Relation of ventilatory impairment and of chronic mucus hypersecretion to mortality from obstructive lung disease and from all causes.
    Thorax. 1990 Aug;45(8):579-85 PMID: 2402719
  7. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  8. Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family members.
    Physiol Genomics. 2006 May 16;25(3):502-13 PMID: 16569774
  9. Niflumic acid suppresses interleukin-13-induced asthma phenotypes.
    Am J Respir Crit Care Med. 2006 Jun 1;173(11):1216-21 PMID: 16528019
  10. Immunogenetic programs for viral induction of mucous cell metaplasia.
    Am J Respir Cell Mol Biol. 2006 Jul;35(1):29-39 PMID: 16543602
  11. Quantitative microsatellite analysis to delineate the commonly deleted region 1p22.3 in mantle cell lymphomas.
    Genes Chromosomes Cancer. 2006 Oct;45(10):883-92 PMID: 16830336
  12. Potential misclassification of causes of death from COPD.
    Eur Respir J. 2006 Oct;28(4):781-5 PMID: 16807258
  13. The putative chloride channel hCLCA2 has a single C-terminal transmembrane segment.
    J Biol Chem. 2006 Oct 6;281(40):29448-54 PMID: 16873362
  14. Both cleavage products of the mCLCA3 protein are secreted soluble proteins.
    J Biol Chem. 2006 Oct 6;281(40):30072-80 PMID: 16895902
  15. Cloning and heterologous expression of a Ca2+-activated chloride channel isoform from rat brain.
    Biol Pharm Bull. 2006 Nov;29(11):2168-73 PMID: 17077509
  16. Decoding NMDA receptor signaling: identification of genomic programs specifying neuronal survival and death.
    Neuron. 2007 Feb 15;53(4):549-62 PMID: 17296556
  17. LPS-induced mucin expression in human sinus mucosa can be attenuated by hCLCA inhibitors.
    J Endotoxin Res. 2007;13(2):109-16 PMID: 17621552
  18. Survival after lung volume reduction in chronic obstructive pulmonary disease: insights from small airway pathology.
    Am J Respir Crit Care Med. 2007 Sep 1;176(5):454-9 PMID: 17556723
  19. Increased expression of human calcium-activated chloride channel 1 gene is correlated with mucus overproduction in Chinese asthmatic airway.
    Cell Biol Int. 2007 Nov;31(11):1388-95 PMID: 17698377
  20. Complete inhibition of allergic airway inflammation and remodelling in quadruple IL-4/5/9/13-/- mice.
    Clin Exp Allergy. 2007 Oct;37(10):1427-35 PMID: 17883722
  21. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids.
    Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15858-63 PMID: 17898169
  22. Targeting integrin beta4 for cancer and anti-angiogenic therapy.
    Trends Pharmacol Sci. 2007 Oct;28(10):506-11 PMID: 17822782
  23. Expression of three distinct families of calcium-activated chloride channel genes in the mouse dorsal root ganglion.
    Neurosci Bull. 2007 Sep;23(5):293-9 PMID: 17952139
  24. Induction of mouse Ca(2+)-sensitive chloride channel 2 gene during involution of mammary gland.
    Biochem Biophys Res Commun. 1999 Nov 2;264(3):933-7 PMID: 10544033
  25. Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2.
    Cancer Res. 1999 Nov 1;59(21):5488-91 PMID: 10554024
  26. Quantitative trait locus mapping of airway responsiveness to chromosomes 6 and 7 in inbred mice.
    Am J Physiol. 1999 Dec;277(6 Pt 1):L1118-23 PMID: 10600881
  27. Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice.
    Am J Respir Cell Mol Biol. 2000 Oct;23(4):537-45 PMID: 11017920
  28. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes.
    J Mol Biol. 2001 Jan 19;305(3):567-80 PMID: 11152613
  29. Isolation and characterization of a Ca(2+)-activated chloride channel from human corneal epithelium.
    Curr Eye Res. 2000 Dec;21(6):918-25 PMID: 11262615
  30. Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma.
    Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5175-80 PMID: 11296262
  31. The breast cancer beta 4 integrin and endothelial human CLCA2 mediate lung metastasis.
    J Biol Chem. 2001 Jul 6;276(27):25438-46 PMID: 11320086
  32. Spontaneous Ca2+ activated Cl- currents in isolated urethral smooth muscle cells.
    J Urol. 2001 Sep;166(3):1161-6 PMID: 11490316
  33. Tumor suppression by a proapoptotic calcium-activated chloride channel in mammary epithelium.
    J Biol Chem. 2001 Nov 2;276(44):40510-7 PMID: 11483609
  34. Characterization of a calcium-activated chloride channel as a shared target of Th2 cytokine pathways and its potential involvement in asthma.
    Am J Respir Cell Mol Biol. 2001 Oct;25(4):486-91 PMID: 11694454
  35. Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease.
    Am J Respir Crit Care Med. 2001 Nov 1;164(9):1618-23 PMID: 11719299
  36. A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma.
    J Allergy Clin Immunol. 2002 Feb;109(2):246-50 PMID: 11842292
  37. Ca(2+)-activated Cl(-) channels: a newly emerging anion transport family.
    Pflugers Arch. 2001;443 Suppl 1:S107-10 PMID: 11845314
  38. Genetic analysis of antigen-induced airway manifestations of asthma using recombinant congenic mouse strains.
    Chest. 2002 Mar;121(3 Suppl):13S PMID: 11893654
  39. BLAT--the BLAST-like alignment tool.
    Genome Res. 2002 Apr;12(4):656-64 PMID: 11932250
  40. Expression of respiratory mucins in fatal status asthmaticus and mild asthma.
    Histopathology. 2002 Apr;40(4):367-73 PMID: 11943022
  41. Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease.
    Am J Hum Genet. 2002 May;70(5):1229-39 PMID: 11914989
  42. Increased expression of the human Ca2+-activated Cl- channel 1 (CaCC1) gene in the asthmatic airway.
    Am J Respir Crit Care Med. 2002 Apr 15;165(8):1132-6 PMID: 11956057
  43. Molecular and functional characterization of a murine calcium-activated chloride channel expressed in smooth muscle.
    J Biol Chem. 2002 May 24;277(21):18586-91 PMID: 11896056
  44. The murine mCLCA3 (alias gob-5) protein is located in the mucin granule membranes of intestinal, respiratory, and uterine goblet cells.
    J Histochem Cytochem. 2002 Jun;50(6):829-38 PMID: 12019299
  45. Real-time RT-PCR quantitation of mCLCA1 and mCLCA2 reveals differentially regulated expression in pre- and postnatal murine tissues.
    Histochem Cell Biol. 2002 Jul;118(1):11-7 PMID: 12122442
  46. Viral induction of a chronic asthma phenotype and genetic segregation from the acute response.
    J Clin Invest. 2002 Jul;110(2):165-75 PMID: 12122108
  47. Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma.
    Nat Med. 2002 Aug;8(8):885-9 PMID: 12091879
  48. Focal adhesion kinase activated by beta(4) integrin ligation to mCLCA1 mediates early metastatic growth.
    J Biol Chem. 2002 Sep 13;277(37):34391-400 PMID: 12110680
  49. Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere.
    Mol Biol Cell. 2002 Oct;13(10):3369-87 PMID: 12388743
  50. Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case-control study.
    Thorax. 2003 Jan;58(1):37-42 PMID: 12511718
  51. Equine recurrent airway obstruction: pathogenesis, diagnosis, and patient management.
    Vet Clin North Am Equine Pract. 2002 Dec;18(3):453-67, vi PMID: 12516928
  52. A calcium-activated chloride channel blocker inhibits goblet cell metaplasia and mucus overproduction.
    Novartis Found Symp. 2002;248:150-65; discussion 165-70, 277-82 PMID: 12568493
  53. Modulation of Ca2+-activated Cl- secretion by basolateral K+ channels in human normal and cystic fibrosis airway epithelia.
    Pediatr Res. 2003 Apr;53(4):608-18 PMID: 12612194
  54. Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease.
    Hum Mol Genet. 2003 May 15;12(10):1199-210 PMID: 12719384
  55. Recurrent airway obstruction--heaves.
    Vet Clin North Am Equine Pract. 2003 Apr;19(1):63-86, vi PMID: 12747662
  56. Mucin genes in horse airways: MUC5AC, but not MUC2, may play a role in recurrent airway obstruction.
    Equine Vet J. 2003 May;35(3):252-7 PMID: 12755427
  57. Determinants of prognosis of COPD in the elderly: mucus hypersecretion, infections, cardiovascular comorbidity.
    Eur Respir J Suppl. 2003 May;40:10s-14s PMID: 12762568
  58. Increased expression of interleukin-9, interleukin-9 receptor, and the calcium-activated chloride channel hCLCA1 in the upper airways of patients with cystic fibrosis.
    Laryngoscope. 2003 Jun;113(6):1037-42 PMID: 12782818
  59. Evaluation of a quantitative real-time PCR for the detection of respiratory syncytial virus in pulmonary diseases.
    Eur Respir J. 2003 Jun;21(6):944-51 PMID: 12797486
  60. Characterization of airway plugging in fatal asthma.
    Am J Med. 2003 Jul;115(1):6-11 PMID: 12867228
  61. Therapy for chronic obstructive pulmonary disease in the 21st century.
    Drugs. 2003;63(19):1973-98 PMID: 12962514
  62. The interacting binding domains of the beta(4) integrin and calcium-activated chloride channels (CLCAs) in metastasis.
    J Biol Chem. 2003 Dec 5;278(49):49406-16 PMID: 14512419
  63. Niflumic acid inhibits ATP-stimulated exocytosis in a mucin-secreting epithelial cell line.
    Am J Physiol Cell Physiol. 2004 Feb;286(2):C247-55 PMID: 14522823
  64. Calcium-activated chloride channel-2 in human epithelia.
    J Histochem Cytochem. 2004 Mar;52(3):415-8 PMID: 14966209
  65. CLCA2 tumour suppressor gene in 1p31 is epigenetically regulated in breast cancer.
    Oncogene. 2004 Feb 19;23(7):1474-80 PMID: 14973555
  66. CLCA1 gene polymorphisms in chronic obstructive pulmonary disease.
    J Med Genet. 2004 Mar;41(3):e27 PMID: 14985398
  67. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence.
    Proteomics. 2004 Jun;4(6):1633-49 PMID: 15174133
  68. Talniflumate (Genaera).
    Curr Opin Investig Drugs. 2004 May;5(5):557-62 PMID: 15202731
  69. The nature of small-airway obstruction in chronic obstructive pulmonary disease.
    N Engl J Med. 2004 Jun 24;350(26):2645-53 PMID: 15215480
  70. Expression of HCLCA1 in cystic fibrosis lungs is associated with mucus overproduction.
    Eur Respir J. 2004 Jun;23(6):846-50 PMID: 15218996
  71. Improved prediction of signal peptides: SignalP 3.0.
    J Mol Biol. 2004 Jul 16;340(4):783-95 PMID: 15223320
  72. Clustal W and Clustal X version 2.0.
    Bioinformatics. 2007 Nov 1;23(21):2947-8 PMID: 17846036
  73. A soluble secreted glycoprotein (eCLCA1) is overexpressed due to goblet cell hyperplasia and metaplasia in horses with recurrent airway obstruction.
    Vet Pathol. 2007 Nov;44(6):901-11 PMID: 18039903
  74. Hospital admission rates among men and women with symptoms of chronic bronchitis and airflow limitation corresponding to the GOLD stages of chronic obstructive pulmonary disease--a population-based study.
    Respir Med. 2008 Jan;102(1):109-20 PMID: 17928213
  75. Amelioration of cystic fibrosis intestinal mucous disease in mice by restoration of mCLCA3.
    Gastroenterology. 2007 Dec;133(6):1928-37 PMID: 18054564
  76. Ensembl 2008.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D707-14 PMID: 18000006
  77. Database resources of the National Center for Biotechnology Information.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D13-21 PMID: 18045790
  78. The UCSC Genome Browser Database: 2008 update.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D773-9 PMID: 18086701
  79. A physical map of the bovine genome.
    Genome Biol. 2007;8(8):R165 PMID: 17697342
  80. Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre.
    Proteins. 2008 Feb 15;70(3):611-25 PMID: 17876813
  81. The horse genome derby: racing from map to whole genome sequence.
    Chromosome Res. 2008;16(1):109-27 PMID: 18274866
  82. RGST - Rat Gene Symbol Tracker, a database for defining official rat gene symbols.
    BMC Genomics. 2008;9:29 PMID: 18215257
  83. Murine mCLCA6 is an integral apical membrane protein of non-goblet cell enterocytes and co-localizes with the cystic fibrosis transmembrane conductance regulator.
    J Histochem Cytochem. 2008 May;56(5):495-509 PMID: 18285349
  84. What everybody should know about the rat genome and its online resources.
    Nat Genet. 2008 May;40(5):523-7 PMID: 18443589
  85. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.
    Nat Med. 2008 Jun;14(6):633-40 PMID: 18488036
  86. The Jpred 3 secondary structure prediction server.
    Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W197-201 PMID: 18463136
  87. mCLCA4 ER processing and secretion requires luminal sorting motifs.
    Am J Physiol Cell Physiol. 2008 Jul;295(1):C279-87 PMID: 18495813
  88. Isolation and functional reconstitution of a 38-kDa chloride channel protein from bovine tracheal membranes.
    J Biol Chem. 1991 Mar 15;266(8):4782-8 PMID: 1705933
  89. Mediation of lung metastasis of murine melanomas by a lung-specific endothelial cell adhesion molecule.
    Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9568-72 PMID: 1946371
  90. Immunopurification and structural analysis of a putative epithelial Cl- channel protein isolated from bovine trachea.
    J Biol Chem. 1992 Feb 25;267(6):3618-25 PMID: 1371273
  91. Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis.
    J Clin Invest. 1992 Jun;89(6):1718-24 PMID: 1601982
  92. ALSCRIPT: a tool to format multiple sequence alignments.
    Protein Eng. 1993 Jan;6(1):37-40 PMID: 8433969
  93. Correlation between the lung distribution patterns of Lu-ECAM-1 and melanoma experimental metastases.
    Int J Cancer. 1993 Feb 20;53(4):628-33 PMID: 8436436
  94. [Bronchial reactivity to methacholine and serotonin in six inbred mouse strains].
    Arerugi. 1993 Jan;42(1):42-7 PMID: 8457166
  95. Phosphorylation and activation of a bovine tracheal anion channel by Ca2+/calmodulin-dependent protein kinase II.
    J Biol Chem. 1994 Oct 28;269(43):26642-50 PMID: 7929397
  96. Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice.
    Exp Lung Res. 1995 Jul-Aug;21(4):503-18 PMID: 7588439
  97. Chronic mucus hypersecretion in COPD and death from pulmonary infection.
    Eur Respir J. 1995 Aug;8(8):1333-8 PMID: 7489800
  98. Cloning of an epithelial chloride channel from bovine trachea.
    J Biol Chem. 1995 Dec 29;270(52):31016-26 PMID: 8537359
  99. Strain and route differences in airway responsiveness to acetylcholine in mice.
    Res Commun Mol Pathol Pharmacol. 1995 Oct;90(1):169-72 PMID: 8581342
  100. Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group.
    Am J Respir Crit Care Med. 1996 May;153(5):1530-5 PMID: 8630597
  101. Modulation of membrane currents and mechanical activity by niflumic acid in rat vascular smooth muscle.
    Eur J Pharmacol. 1996 Dec 12;317(1):165-74 PMID: 8982733
  102. Cloning and characterization of lung-endothelial cell adhesion molecule-1 suggest it is an endothelial chloride channel.
    J Biol Chem. 1997 Oct 31;272(44):27853-61 PMID: 9346932
  103. Murine strain differences in airway inflammation caused by diesel exhaust particles.
    Eur Respir J. 1998 Feb;11(2):291-8 PMID: 9551727
  104. Molecular and functional characterization of a calcium-sensitive chloride channel from mouse lung.
    J Biol Chem. 1998 Nov 27;273(48):32096-101 PMID: 9822685
  105. Genomic cloning, molecular characterization, and functional analysis of human CLCA1, the first human member of the family of Ca2+-activated Cl- channel proteins.
    Genomics. 1998 Dec 1;54(2):200-14 PMID: 9828122
  106. Cloning and identification of the gene gob-5, which is expressed in intestinal goblet cells in mice.
    Biochem Biophys Res Commun. 1999 Feb 16;255(2):347-51 PMID: 10049711
  107. Characterization of a murine gene homologous to the bovine CaCC chloride channel.
    Gene. 1999 Mar 4;228(1-2):181-8 PMID: 10072771
  108. Molecular cloning and biochemical characterization of a truncated, secreted member of the human family of Ca2+-activated Cl- channels.
    Biochim Biophys Acta. 1999 Mar 19;1444(3):418-23 PMID: 10095065
  109. Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland.
    Am J Physiol. 1999 Jun;276(6 Pt 1):C1261-70 PMID: 10362588
  110. Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea.
    FEBS Lett. 1999 Jul 23;455(3):295-301 PMID: 10437792
  111. Prediction of potential GPI-modification sites in proprotein sequences.
    J Mol Biol. 1999 Sep 24;292(3):741-58 PMID: 10497036
  112. Genetic variability in pulmonary physiological, cellular, and antibody responses to antigen in mice.
    Am J Respir Crit Care Med. 1999 Oct;160(4):1150-6 PMID: 10508801
  113. Adenosine up-regulation of the mucin gene, MUC2, in asthma.
    FASEB J. 2004 Nov;18(14):1770-2 PMID: 15345696
  114. OBSERVATIONS ON HEAVES. AN ASTHMA-LIKE SYNDROME IN THE HORSE.
    J Allergy. 1964 Jul-Aug;35:322-30 PMID: 14193184
  115. The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis.
    Hum Genet. 2004 Nov;115(6):483-91 PMID: 15490240
  116. Dynamics of Ca2+-dependent Cl- channel modulation by niflumic acid in rabbit coronary arterial myocytes.
    Mol Pharmacol. 2005 Jan;67(1):163-73 PMID: 15465927
  117. Niflumic acid and MSI-2216 reduce TNF-alpha-induced mucin expression in human airway mucosa.
    J Allergy Clin Immunol. 2005 Feb;115(2):266-71 PMID: 15696080
  118. The quantification of hCLCA2 and colocalisation with integrin beta4 in stratified human epithelia.
    Acta Histochem. 2005;106(6):421-5 PMID: 15707651
  119. Calcium-activated chloride channels.
    Annu Rev Physiol. 2005;67:719-58 PMID: 15709976
  120. Respiratory viral infections in patients with chronic, obstructive pulmonary disease.
    J Infect. 2005 May;50(4):322-30 PMID: 15845430
  121. Respiratory syncytial virus infection in elderly and high-risk adults.
    N Engl J Med. 2005 Apr 28;352(17):1749-59 PMID: 15858184
  122. Structure and function of CLCA proteins.
    Physiol Rev. 2005 Jul;85(3):1061-92 PMID: 15987802
  123. hCLCA1 and mCLCA3 are secreted non-integral membrane proteins and therefore are not ion channels.
    J Biol Chem. 2005 Jul 22;280(29):27205-12 PMID: 15919655
  124. Cloning and expression of Ca2+-activated chloride channel from rat brain.
    Biochem Biophys Res Commun. 2005 Aug 26;334(2):569-76 PMID: 16023076
  125. Overexpression of eCLCA1 in small airways of horses with recurrent airway obstruction.
    J Histochem Cytochem. 2005 Aug;53(8):1011-21 PMID: 15879574
  126. Gob-5 is not essential for mucus overproduction in preclinical murine models of allergic asthma.
    Am J Respir Cell Mol Biol. 2005 Sep;33(3):303-14 PMID: 15947424
  127. Temporal regulation of cytokine mRNA expression in equine recurrent airway obstruction.
    Vet Immunol Immunopathol. 2005 Oct 18;108(1-2):237-45 PMID: 16098607
  128. Mortality in GOLD stages of COPD and its dependence on symptoms of chronic bronchitis.
    Respir Res. 2005;6:98 PMID: 16120227
  129. Characterization of CLCA protein expressed in ductal cells of rat salivary glands.
    Biochim Biophys Acta. 2005 Sep 15;1715(2):132-44 PMID: 16137643
  130. Blue native/SDS-PAGE analysis reveals reduced expression of the mClCA3 protein in cystic fibrosis knock-out mice.
    Mol Cell Proteomics. 2005 Nov;4(11):1762-75 PMID: 16099848
  131. Differential regulation of MUC5AC/Muc5ac and hCLCA-1/mGob-5 expression in airway epithelium.
    Am J Respir Cell Mol Biol. 2005 Dec;33(6):523-30 PMID: 16151054
  132. Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals.
    J Clin Invest. 2006 Feb;116(2):309-21 PMID: 16453019
  133. Talniflumate increases survival in a cystic fibrosis mouse model of distal intestinal obstructive syndrome.
    J Pharmacol Exp Ther. 2006 Apr;317(1):275-83 PMID: 16354791
  134. Novel conserved hydrolase domain in the CLCA family of alleged calcium-activated chloride channels.
    Proteins. 2006 May 15;63(3):424-39 PMID: 16470849
  135. Relationship between calcium-activated chloride channel 1 and MUC5AC in goblet cell hyperplasia induced by interleukin-13 in human bronchial epithelial cells.
    Respiration. 2006;73(3):347-59 PMID: 16465045
Article Info
Journal
Annual review of physiology
Abbr.
Annu Rev Physiol
ISSN
1545-1585
DOI
10.1146/annurev.physiol.010908.163253
Published
2009-00-00
Pages
425-49
Language
English
Region
United States
NLM ID
0370600
PMCID
PMC4017675
Subset
IM
Grants
NHLBI NIH HHS · K08 HL083095 · United States
External Links
PubMed source DOI: 10.1146/annurev.physiol.010908.163253 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2