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)

To identify changes in gene expression associated with emphysema, differential display was used to compare RNA extracted from emphysematous lung with that of unused donor tissue taken at the time of transplant. Two expressed clones with sequence homology to the 3' UTR of the murine flotillin-1 cDNA were identified. Flotillin-1 is a plasma membrane protein, which has been associated with detergent-insoluble glycolipid-rich domains and the formation of caveolae. One clone was 95 bp longer than the other. It arose from the use of a second polyadenylation signal and its existence was not due to differential expression nor to polymorphisms in the human flotillin-1 sequence. The 1839 bp human flotillin-1 sequence was completed by 5' RACE from a lung cDNA library. The human mRNA has a 1.9 kbase transcript being highly expressed in brain, heart and lung. The single copy flotillin-1 gene is located at 6p21.3 in the MHC class I region and consists of 13 exons over 15 kb. The ORF encodes a 427 residue protein with a molecular mass 47355 Da, and an isoelectric point 7.08. Human flotillin-1 has a 98% identity with the murine protein and a 47% identity with human flotillin-2. Flotillin-1 belongs to the Band 7.2/stomatin protein family, possessing a hydrophobic N-terminal region, predicted to form a single, outside to inside, transmembrane domain. The long central alpha-helical domain may form a coiled-coil. We have isolated and characterised a cDNA encoding the human flotillin-1 gene, which may play an important role in raft formation.
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PMID:Flotillin-1: gene structure: cDNA cloning from human lung and the identification of alternative polyadenylation signals. 1116 32

Cadmium (Cd) is a known human lung carcinogen. In addition, Cd exposure is associated with several lung diseases including emphysema, chronic obstructive pulmonary disease (COPD), asthma and fibrosis. Although earlier studies have identified several processes dysregulated by Cd exposure, the underlying mechanisms remain unclear. Here, we examined the transcriptome of lung epithelial cells exposed to Cd to understand the molecular basis of Cd-induced diseases. Computational analysis of the transcriptome predicted a significant number of Cd-upregulated genes to be targets of miR-30 family miRNAs. Experimental validation showed downregulation of all the miR-30 family members in Cd exposed cells. We found SNAIL, an EMT master regulator, to be the most upregulated among the miR-30 targets. Furthermore, we found decrease in the levels of epithelial marker E- cadherin (CDH1) and increase in the levels of mesenchymal markers, ZEB1 and vimentin. This suggested induction of EMT in Cd exposed cells. Luciferase reporter assays showed that miR-30 repressed SNAIL by directly targeting its 3' UTR. Over expression of miR-30e and transfection of miR-30e mimics reduced Cd-induced SNAIL upregulation. Our results suggest that miR-30 negatively regulates SNAIL in lung epithelial cells and that Cd-induced downregulation of miR-30 relieves this repression, resulting in SNAIL upregulation and EMT induction. EMT plays a major role in many diseases associated with Cd exposure including fibrosis, COPD, and cancer and metastasis. Therefore, our identification of miR-30 downregulation in Cd exposed cells and the consequent activation of SNAIL provides important mechanistic insights into lung diseases associated with Cd exposure.
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PMID:Cadmium exposure upregulates SNAIL through miR-30 repression in human lung epithelial cells. 3099 37