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Abstract: TH-PO924

Fibroblast-Specific p90RSK Promotes Epithelial Transdifferentiation and Kidney Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms


  • Lin, Ling, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Shi, Chaowen, Penn State University College of Medicine, Hershey, Pennsylvania, United States
  • Hu, Kebin, Penn State University College of Medicine, Hershey, Pennsylvania, United States

Epithelial integrity and interactions between epithelial cells and other kidney cells play important roles in maintaining normal kidney structure and environment. p90RSK, a serine/threonine kinase, is recently shown to promote diabetic endothelial dysfunction and atherosclerosis, however, the role of p90RSK in chronic kidney disease remains largely unknown.


We generated a novel fibroblast-specific p90RSK transgenic mouse (RSK-Tg) and established a fibroblast-epitheial 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-epitheial interactions and kidney fibrosis.


First, we examined the expression of phospho-specific and total p90RSK during the course of chronic kidney injury in the classic unilateral ureter obstruction (UUO) model. It’s found that p90RSK is dramatically activated, largely in the interstitial FSP-1-positive fibroblasts. We generated fibroblast-specific p90RSK transgenic mouse, RSK-Tg, and found that this mouse has normal phenotype as the littermate control (RSK-wt). However, after UUO injury, RSK-Tg mice display significantly worse tubular damage, decreased E-cadherin expression, and de novo activation of alpha-SMA, as well as increased fibrosis, in comparison with their littermates. We further found, in our in vitro fibroblast-epithelial coculture system, that RSK-Tg fibroblasts dramatically induced epithelial activation of β-catenin and its transdifferentiation into myofibroblasts, as indicated by reduced E-cadherin and de novo expression of alpha-SMA. Intriguingly, blocking epithelial β-catenin using siRNA reversed epithelial transdifferentiation.


Thus, it is clear that fibroblast-specific p90RSK activation promotes the epithelial-to-mesenchymal transition (EMT) through activating epithelial β-catenin pathway.


  • NIDDK Support