Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surfactant protein D (SP-D) is a member of the collectin subfamily of C-type lectins, pattern recognition proteins participating in the innate immune response. Gene-targeted mice deficient in SP-D develop abnormalities in surfactant homeostasis, hyperplasia of alveolar epithelial type II cells, and emphysema-like pathology. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is required for terminal differentiation and subsequent activation of alveolar macrophages, including the expression of matrix metalloproteinases and reactive oxygen species, factors thought to contribute to lung remodeling. Type II cells also express the GM-CSF receptor. Thus we hypothesized GM-CSF might mediate some or all of the cellular and structural abnormalities in the lungs of SP-D-deficient mice. To test this, SP-D (D-G+) and GM-CSF (D+G-) single knockout mice as well as double knockout mice deficient for both SP-D and GM-CSF (D-G-) were analyzed by design-based stereology. Compared with wild type, D-G+ as well as D+G- mice showed decreased alveolar numbers, increased alveolar sizes, and decreased alveolar epithelial surface areas. These emphysema-like changes were present to a greater extent in D-G- mice. D-G+ mice developed type II cell hyperplasia and hypertrophy with increased intracellular surfactant pools, whereas D+G- mice had smaller type II cells with decreased intracellular surfactant pools. In contrast to the emphysematous changes, the type II cell alterations were mostly corrected in D-G- mice. These results indicate that GM-CSF-dependent macrophage activity is not necessary for emphysema development in SP-D-deficient mice, but that type II cell metabolism and proliferation are, either directly or indirectly, regulated by GM-CSF in this model.
 ...
PMID:GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice. 1531 May 55

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD. One molecule that has attracted attention as a potentially useful biomarker specifically for the emphysema subpopulation is the soluble receptor for advanced glycation end products (sRAGE). As the soluble isoform of a key proinflammatory signaling receptor, sRAGE acts as a "decoy" for RAGE ligands and prevents their interaction with the receptor. Multiple reports have now linked sRAGE to COPD, and more specifically to emphysema, and evidence is accumulating that this link is likely mechanistic in nature. Here we review the current state of knowledge about sRAGE biology, the mechanistic links to COPD, and the evidence for using it as a biomarker for emphysema. We also discuss sRAGE as a potential target for therapeutic intervention in COPD.
...
PMID:Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung. 2613 89