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Regional differences in susceptibiity of bronchial epithelium to mesenchymal transition and inhibition by the macrolide antibiotic azithromycin

Banerjee, Balarka ; Musk, Michael ; Sutanto, Erika N ; Yerkovich, Stephanie T ; Hopkins, Peter ; Knight, Darryl A ; Lindsey-Temple, Suzanna ; Stick, Stephen M ; Kicic, Anthony ; Chambers, Daniel C Johnson, Rajasingh

PloS one, 2012-12, Vol.7 (12), p.e52309-e52309 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Regional differences in susceptibiity of bronchial epithelium to mesenchymal transition and inhibition by the macrolide antibiotic azithromycin
Autor: Banerjee, Balarka ; Musk, Michael ; Sutanto, Erika N ; Yerkovich, Stephanie T ; Hopkins, Peter ; Knight, Darryl A ; Lindsey-Temple, Suzanna ; Stick, Stephen M ; Kicic, Anthony ; Chambers, Daniel C
Johnson, Rajasingh
Assuntos: Activation ; Adult ; Aged ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Asthma ; Azithromycin ; Azithromycin - pharmacology ; Biology ; Bronchi - cytology ; Bronchi - metabolism ; Bronchi - pathology ; Bronchiolitis obliterans ; Bronchopneumonia ; Cells, Cultured ; Childrens health ; Deoxyribonucleic acid ; DNA ; DNA biosynthesis ; DNA synthesis ; Epithelial cells ; Epithelial-Mesenchymal Transition - drug effects ; Epithelium ; Female ; Fibroblasts ; Fibrosis ; Gene expression ; Growth factors ; Hospitals ; Humans ; Lung Transplantation ; Male ; Medical research ; Medicine ; Mesenchyme ; Middle Aged ; Mycophenolic acid ; Organ transplantation ; Organs ; Patients ; Pulmonary fibrosis ; Receptors, Transforming Growth Factor beta - metabolism ; Regional differences ; Respiratory tract ; Rodents ; Smad3 protein ; Smad3 Protein - metabolism ; Stem cells ; Transforming Growth Factor beta1 - pharmacology ; Transforming growth factor-b1 ; Transforming growth factors ; Transplantation of organs, tissues, etc ; Transplants & implants
É parte de: PloS one, 2012-12, Vol.7 (12), p.e52309-e52309
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: PH DAK SLT SMS AK DCC. Performed the experiments: BB MM ENS STY AK. Analyzed the data: BB STY SMS AK DCC. Wrote the paper: BB DAK SLT SMS AK DCC.
Descrição: Dysregulated repair following epithelial injury is a key forerunner of disease in many organs, and the acquisition of a mesenchymal phenotype by the injured epithelial cells (epithelial to mesenchymal transition, EMT) may serve as a source of fibrosis. The macrolide antibiotic azithromycin and the DNA synthesis inhibitor mycophenolate are in clinical use but their mechanism of action remains unknown in post-transplant bronchiolitis obliterans syndrome (BOS). Here we determined if regional variation in the EMT response to TGFβ1 underlies the bronchiolocentric fibrosis leading to BOS and whether EMT could be inhibited by azithromycin or mycophenolate. We found that small and large airway epithelial cells from stable lung transplant patients underwent EMT when stimulated with TGFβ1, however mesenchymal protein expression was higher and loss of epithelial protein expression more complete in small airway epithelial cells. This regional difference was not mediated by changes in expression of the TGFβRII or Smad3 activation. Azithromycin potentially inhibited EMT in both small and large airway epithelial cells by inhibiting Smad3 expression, but not activation. Collectively, these observations provide a biologic basis for a previously unexplained but widely observed clinical phenomena, and a platform for the development of new approaches to fibrotic diseases.
Editor: United States: Public Library of Science
Idioma: Inglês

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Regional differences in susceptibiity of bronchial epithelium to mesenchymal transition and inhibition by the macrolide antibiotic azithromycin

Banerjee, Balarka ; Musk, Michael ; Sutanto, Erika N ; Yerkovich, Stephanie T ; Hopkins, Peter ; Knight, Darryl A ; Lindsey-Temple, Suzanna ; Stick, Stephen M ; Kicic, Anthony ; Chambers, Daniel C Johnson, Rajasingh

United States: Public Library of Science

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