A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrated that Yap and Taz were normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2-to-AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to an LPS injury prevented AT1 cell regeneration, led to intraalveolar collagen deposition, and resulted in persistent innate inflammation. These findings establish that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.
Gianluca T. DiGiovanni, Wei Han, Taylor P. Sherrill, Chase J. Taylor, David S. Nichols, Natalie M. Geis, Ujjal K. Singha, Carla L. Calvi, A. Scott McCall, Molly M. Dixon, Yang Liu, Ji-Hoon Jang, Sergey S. Gutor, Vasiliy V. Polosukhin, Timothy S. Blackwell, Jonathan A. Kropski, Jason J. Gokey
Usage data is cumulative from September 2023 through August 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 2,999 | 620 |
1,071 | 234 | |
Figure | 628 | 5 |
Supplemental data | 705 | 32 |
Citation downloads | 87 | 0 |
Totals | 5,490 | 891 |
Total Views | 6,381 |
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.