Abstract: FR-PO984
Fibroblast p90RSK Induces Epithelial-to-Mesenchymal Transition Through Oxidative Stress-Mediated β-Catenin Pathway
Session Information
- Pathology and Lab Medicine: Basic
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1601 Pathology and Lab Medicine: Basic
Authors
- Lin, Ling, Penn State University College of Medicine, Hershey, Pennsylvania, United States
- Hu, Kebin, Penn State University College of Medicine, Hershey, Pennsylvania, United States
Background
Healthy kidney structure and environment rely on epithelial integrity and interactions between epithelial cells and other kidney cells. p90RSK, a serine/threonine kinase, is recently shown to promote obstruction-induced kidney fibrosis, however, the underlying mechanism remains largely unknown.
Methods
We generated a novel fibroblast-specific p90RSK transgenic mouse (RSK-Tg) and established a fibroblast-epithelial coculture system using primary kidney fibroblasts from RSK-Tg and RSK-wt mice and human proximal tubular epithelial cells (HKC-8) to investigate the role of p90RSK in fibroblast-epithelial interactions and kidney fibrosis.
Results
It was found that RSK-Tg mouse has similar phenotype as the littermate control (RSK-wt). However, after UUO injury, RSK-Tg mice display significantly increased fibrosis, as demonstrated by renal collagen content and FSP-1 abundance, in comparison with their littermates. We further found that RSK-Tg mice display decreased E-cadherin, increased MMP-9, and de novo activation of alpha-SMA, indicating enhanced epithelial-to-mesenchymal transition (EMT), which was also visualized by double fluorescence staining of FSP-1 and lectin. Moreover, it was found, in our in vitro fibroblast-epithelial coculture system, that RSK-Tg fibroblasts consistently produce excessive H2O2 causing epithelial oxidative stress and inducing β-catenin nuclear translocation. Of note, blockade of reactive oxygen species (ROS) or β-catenin abolished fibroblast p90RSK-mediated EMT.
Conclusion
Thus, it is clear that fibroblast p90RSK induces EMT through oxidative stress-mediated β-catenin pathway.
Funding
- NIDDK Support