Usage Information
Citation Information: JCI Insight. 2018;3(16):e99543. https://doi.org/10.1172/jci.insight.99543.
Abstract
ER stress in type II alveolar epithelial cells (AECs) is common in idiopathic pulmonary fibrosis (IPF), but the contribution of ER stress to lung fibrosis is poorly understood. We found that mice deficient in C/EBP homologous protein (CHOP), an ER stress–regulated transcription factor, were protected from lung fibrosis and AEC apoptosis in 3 separate models where substantial ER stress was identified. In mice treated with repetitive intratracheal bleomycin, we identified localized hypoxia in type II AECs as a potential mechanism explaining ER stress. To test the role of hypoxia in lung fibrosis, we treated mice with bleomycin, followed by exposure to 14% O2, which exacerbated ER stress and lung fibrosis. Under these experimental conditions, CHOP–/– mice, but not mice with epithelial HIF (HIF1/HIF2) deletion, were protected from AEC apoptosis and fibrosis. In vitro studies revealed that CHOP regulates hypoxia-induced apoptosis in AECs via the inositol-requiring enzyme 1α (IRE1α) and the PKR-like ER kinase (PERK) pathways. In human IPF lungs, CHOP and hypoxia markers were both upregulated in type II AECs, supporting a conclusion that localized hypoxia results in ER stress–induced CHOP expression, thereby augmenting type II AEC apoptosis and potentiating lung fibrosis.
Authors
Ankita Burman, Jonathan A. Kropski, Carla L. Calvi, Ana P. Serezani, Bruno D. Pascoalino, Wei Han, Taylor Sherrill, Linda Gleaves, William E. Lawson, Lisa R. Young, Timothy S. Blackwell, Harikrishna Tanjore
Usage data is cumulative from March 2022 through March 2023.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,415 | 284 |
| 128 | 71 | |
| Figure | 572 | 2 |
| Table | 32 | 0 |
| Supplemental data | 37 | 13 |
| Citation downloads | 34 | 0 |
| Totals | 2,218 | 370 |
| Total Views | 2,588 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
