Siegfried Alberti
Research Interests
Siegfried Alberti has a total of 14 co-authors. Here are the top co-authors by number of shared publications:
- Alfred Nordheim
Department of Molecular Biology, Interfaculty Institute of Cell Biology, University of Tübingen, 72076 Tübingen, Germany
1 shared publication - Amanda L. Tatler
School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK
1 shared publication - Anthony Habgood
University of Nottingham
1 shared publication - Burns C. Blaxall
From The Heart Institute, Division of Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, OH.
1 shared publication - Chloe Wilkinson
University of Nottingham
1 shared publication - Fiona Oakley
Newcastle Fibrosis Research Group, Bioscience Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
1 shared publication
Latest Publications
- Open Access
Loss of ELK1 has differential effects on age-dependent organ fibrosis and integrin expression
ETS domain-containing protein-1 (ELK1) is a transcriptional repressor important in regulating αvβ6 integrin expression. αvβ6 integrins activate the profibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and are increased in the alveolar epithelium in Idiopathic Pulmonary Fibrosis (IPF). IPF is a disease associated with ageing and therefore we hypothesised that aged animals lacking Elk1 globally would develop spontaneous fibrosis in organs where αvβ6-mediated TGFβ 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 3α1, 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 genes 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 cells and murine lung slices to cigarette smoke extract which lead to reduced ELK1 expression which may 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.
Open AccessLoss of ELK1 has differential effects on age-dependent organ fibrosis and integrin expression
ETS domain-containing protein-1 (ELK1) is a transcriptional repressor important in regulating αvβ6 integrin expression. αvβ6 integrins activate the profibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and are increased in the alveolar epithelium in Idiopathic Pulmonary Fibrosis (IPF). IPF is a disease associated with ageing and therefore we hypothesised that aged animals lacking Elk1 globally would develop spontaneous fibrosis in organs where αvβ6-mediated TGFβ 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 3α1, 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 genes 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 cells and murine lung slices to cigarette smoke extract which lead to reduced ELK1 expression which may 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.