| First Author | Cairns JT | Year | 2020 |
| Journal | Int J Biochem Cell Biol | Volume | 120 |
| Pages | 105668 | PubMed ID | 31877385 |
| Mgi Jnum | J:297544 | Mgi Id | MGI:6472092 |
| Doi | 10.1016/j.biocel.2019.105668 | Citation | Cairns JT, et al. (2020) Loss of ELK1 has differential effects on age-dependent organ fibrosis. Int J Biochem Cell Biol 120:105668 |
| abstractText | ETS domain-containing protein-1 (ELK1) is a transcription factor important in regulating alphavbeta6 integrin expression. alphavbeta6 integrins activate the profibrotic cytokine Transforming Growth Factor beta1 (TGFbeta1) and are increased in the alveolar epithelium in idiopathic pulmonary fibrosis (IPF). IPF is a disease associated with aging and therefore we hypothesised that aged animals lacking Elk1 globally would develop spontaneous fibrosis in organs where alphavbeta6 mediated TGFbeta activation has been implicated. Here we identify that Elk1-knockout (Elk1(-/0)) mice aged to one year developed spontaneous fibrosis in the absence of injury in both the lung and the liver but not in the heart or kidneys. The lungs of Elk1(-/0) aged mice demonstrated increased collagen deposition, in particular collagen 3alpha1, located in small fibrotic foci and thickened alveolar walls. Despite the liver having relatively low global levels of ELK1 expression, Elk1(-/0) animals developed hepatosteatosis and fibrosis. The loss of Elk1 also had differential effects on Itgb1, Itgb5 and Itgb6 expression in the four organs potentially explaining the phenotypic differences in these organs. To understand the potential causes of reduced ELK1 in human disease we exposed human lung epithelial cells and murine lung slices to cigarette smoke extract, which lead to reduced ELK1 expression andmay explain the loss of ELK1 in human disease. These data support a fundamental role for ELK1 in protecting against the development of progressive fibrosis via transcriptional regulation of beta integrin subunit genes, and demonstrate that loss of ELK1 can be caused by cigarette smoke. |
