Adenosine and osteopontin contribute to the development of chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a major health concern. Adenosine, a signaling molecule generated in response to cell stress, contributes to the pathogenesis of COPD. An established model of adenosine-mediated lung injury is the adenosine deaminase-deficient (Ada(-/-)) mouse. Osteopontin (OPN) is a chemokine that is produced following injury and is implicated in a variety of human pathologies, but its expression and role in the pathogenesis of COPD have not been examined. To investigate the role of OPN in a model of COPD, Ada(-/-) double-knockout mice were generated, and inflammation and air-space enlargement endpoints were examined. Results demonstrate that Ada(-/-) mice exhibit OPN-dependent neutrophilia, alveolar air-space enlargement, and increases in mediators of air-space enlargement. Furthermore, we demonstrate that patients with COPD have increased OPN expression within distal airways in association with clinical airway obstruction. These results suggest that OPN represents a novel biomarker and therapeutic target for patients with COPD.
Schneider
Daniel J
DJ
Department of Biochemistry and Molecular Biology, The University of Texas-Houston Medical School, 6431 Fannin Blvd., Houston, TX 77030, USA.
Lindsay
Janci C
JC
Zhou
Yang
Y
Molina
Jose G
JG
Blackburn
Michael R
MR
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000172:deficiency / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D004646:Emphysema / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism
D012333:RNA, Messenger; D043704:Receptor, Adenosine A2B; C506895:SPP1 protein, human; C506896:Spp1 protein, mouse; D053495:Osteopontin; D000243:Adenosine Deaminase; D000241:Adenosine