The role of club cell phenoconversion and migration in idiopathic pulmonary fibrosis
| Autor: | Neha Muthavarapu, Lee C. Tan, Lakshmi Galam, Jutaro Fukumoto, Jayanthraj Gone, Nima Hosseinian, Andrew J. Cooke, Travis Herrin, Mason Breitzig, Ruan Cox, Sanjay Mahendrasah, Young Ae Cho, Joseph Leung, Yashwant Pathak, Richard F. Lockey, Venkata Ramireddy Narala, Priyanshi Patel, Narasaiah Kolliputi, Alexander Czachor, Ramani Soundararajan |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Aging Pathology medicine.medical_specialty migration Pathogenesis 03 medical and health sciences Idiopathic pulmonary fibrosis Pulmonary Disease Chronic Obstructive 0302 clinical medicine Cell Movement Medicine Humans club cell secretory protein (CCSP) Bronchiolar epithelium Lung business.industry Claudin10/Cldn10/Claudin-10 Lung fibrosis Cell Biology respiratory system medicine.disease Actins Idiopathic Pulmonary Fibrosis 3. Good health respiratory tract diseases 030104 developmental biology Club cell Secretory protein 030228 respiratory system Pleomorphism (cytology) Alveolar Epithelial Cells Claudins Immunohistochemistry club cells idiopathic pulmonary fibrosis (IPF) business Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) is an age-related multifactorial disease featuring non-uniform lung fibrosis. The decisive cellular events at early stages of IPF are poorly understood. While the involvement of club cells in IPF pathogenesis is unclear, their migration has been associated with lung fibrosis. In this study, we labeled club cells immunohistochemically in IPF lungs using a club cell marker Claudin-10 (Cldn10), a unique protein based on the recent report which demonstrated that the appearance of Cldn10 in developing and repairing lungs precedes other club cell markers including club cell secretory protein (CCSP). Cldn10-positive cells in IPF lungs displayed marked pleomorphism and were found in varied arrangements, suggesting their phenoconversion. These results were corroborated by immunogold labeling for Cldn10. Further, immunohistochemical double-labeling for Cldn10 and α-smooth muscle actin (α-SMA) demonstrated that aberrant α-SMA signals are frequently encountered near disorganized Cldn10-positive cells in hyperplastic bronchiolar epithelium and thickened interstitium of IPF lungs. Collectively, these data indicate that club cells actively participate in the initiation and progression of IPF through phenoconversion involving the acquisition of proliferative and migratory abilities. Thus, our new findings open the possibility for club cell-targeted therapy to become a strategic option for the treatment of IPF. |
| Databáze: | OpenAIRE |
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