TRIM72 promotes alveolar epithelial cell membrane repair and ameliorates lung fibrosis
Autor: | Dianhua Jiang, Rolf D. Hubmayr, Xiaoli Zhao, Jeremy Herrera, Hong Long Ji, Ian Pepper, Robell Morehouse, Nagaraja N. Nagre, Xiaofei Cong, Andrew C. Pearson |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Male Mice 129 Strain Idiopathic pulmonary fibrosis Membrane repair Apoptosis Pathogenesis Tripartite Motif Proteins 03 medical and health sciences Bleomycin Mice 0302 clinical medicine Downregulation and upregulation Fibrosis Medicine Animals Humans Lung lcsh:RC705-779 Mice Knockout business.industry Regeneration (biology) Research lcsh:Diseases of the respiratory system respiratory system medicine.disease Recombinant Proteins respiratory tract diseases 030104 developmental biology medicine.anatomical_structure HEK293 Cells Cell culture 030220 oncology & carcinogenesis Alveolar Epithelial Cells Cancer research Tripartite motif family protein 72 Female business |
Zdroj: | Respiratory Research Respiratory Research, Vol 21, Iss 1, Pp 1-20 (2020) |
ISSN: | 1465-993X 1465-9921 |
Popis: | Background Chronic tissue injury was shown to induce progressive scarring in fibrotic diseases such as idiopathic pulmonary fibrosis (IPF), while an array of repair/regeneration and stress responses come to equilibrium to determine the outcome of injury at the organ level. In the lung, type I alveolar epithelial (ATI) cells constitute the epithelial barrier, while type II alveolar epithelial (ATII) cells play a pivotal role in regenerating the injured distal lungs. It had been demonstrated that eukaryotic cells possess repair machinery that can quickly patch the damaged plasma membrane after injury, and our previous studies discovered the membrane-mending role of Tripartite motif containing 72 (TRIM72) that expresses in a limited number of tissues including the lung. Nevertheless, the role of alveolar epithelial cell (AEC) repair in the pathogenesis of IPF has not been examined yet. Method In this study, we tested the specific roles of TRIM72 in the repair of ATII cells and the development of lung fibrosis. The role of membrane repair was accessed by saponin assay on isolated primary ATII cells and rat ATII cell line. The anti-fibrotic potential of TRIM72 was tested with bleomycin-treated transgenic mice. Results We showed that TRIM72 was upregulated following various injuries and in human IPF lungs. However, TRIM72 expression in ATII cells of the IPF lungs had aberrant subcellular localization. In vitro studies showed that TRIM72 repairs membrane injury of immortalized and primary ATIIs, leading to inhibition of stress-induced p53 activation and reduction in cell apoptosis. In vivo studies demonstrated that TRIM72 protects the integrity of the alveolar epithelial layer and reduces lung fibrosis. Conclusion Our results suggest that TRIM72 protects injured lungs and ameliorates fibrosis through promoting post-injury repair of AECs. |
Databáze: | OpenAIRE |
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